Compositions and methods for the induction of CD8+ T-cells

ABSTRACT

Provided herein are compositions and methods for the induction and/or proliferation of CD8+ T-cells. The disclosure also provides methods of treatment of diseases that can be treated by the induction and/or proliferation of CD8+ T-cells.

RELATED APPLICATIONS

This application is a continuation of international application numberPCT/JP2017/046232, filed Dec. 22, 2017 which claims the benefit under 35U.S.C. § 119(e) of U.S. provisional application No. 62/438,793, filedDec. 23, 2016; U.S. provisional application No. 62/484,607, filed Apr.12, 2017; U.S. provisional application No. 62/491,062, filed Apr. 27,2017; and U.S. provisional application No. 62/574,446, filed Oct. 19,2017. The entire contents of each of these referenced applications areincorporated by reference herein.

TECHNICAL FIELD

The disclosure relates to compositions and methods for the inductionand/or proliferation of CD8+ T-cells. The disclosure also providesmethods of treatment of diseases that can be treated by the inductionand/or proliferation of CD8+ T-cells.

BACKGROUND ART

Animals, including humans, harbor a multitude of microbes (collectivelyreferred to as the microbiota) in anatomical locations including themouth, esophagus, stomach, small intestine, large intestine, caecum,vagina, skin, nasal cavities, ear, and lungs. The human microbiota isresponsible for a multitude of critical processes, including thedevelopment of the immune system, metabolism of carbohydrates, proteinsand xenobiotics, formation and regeneration of the epithelium, fatstorage, production of hormones, production of vitamins, and protectionfrom pathogen infections, among others (See e.g., LeBlanc et al. Curr.Opin. Biotechnol. (2013) 24(2):160-168; Hooper et al. Science (2012)336(60801268-1273; Hughes et al. Am. J. Gastroenterol. (2013)108(7):1066-1074). Modification of the human microbiota, which can becaused by a number of factors such as antibiotic use, excessive hygiene,diet, genetic background or combinations of the above, has beenassociated with a number of unwanted effects including the occurrence ofinfectious diseases (e.g., C. difficile infections), inflammatory,autoimmune and allergic diseases (e.g., ulcerative colitis, Crohn'sdisease, Type I diabetes, food allergies, asthma, rheumatoid arthritis)and metabolic diseases (e.g., Type II diabetes, metabolic syndrome,obesity, malnutrition), and cancer, among others. For instance,modifications of the microbiota can lead to a loss of tolerance againstharmless food antigens or commensal bacterial antigens, subsequentexcessive inflammatory responses, metabolic dysregulation, and damage tothe intestinal tissue, which compromises its ability to serve as abarrier between the gut lumen and the systemic circulation.

Manipulation of the immune response is of great importance in thetreatment of cancer and in vaccination. Cancer therapies that target theimmune system have attained improvements in survival rates. However, alarge percentage of patients do not respond to cancer immunotherapies.Similarly, large population subsets (e.g., the elderly) cannot mountstrong immune responses to vaccines.

Approaches for countering the harmful effects of microbiotamodifications on health are limited, despite the role that suchmodifications play in promoting human pathology. Interventions known tomodulate the microbiota include antibiotics, prebiotics, probiotics andfecal transplants, each of which has limitations and potential adverseeffects. Additional approaches to counter the detrimental effects ofmicrobiome modification on human health are clearly needed. Furthermore,approaches for promoting stronger immune responses to cancer and tovaccines are also needed.

SUMMARY OF INVENTION

The inventors joined the Innovative Advanced Research and DevelopmentSupport Project Incubation Type of Japan Agency for Medical Research andDevelopment (AMED) in 2016, whose Research and Development Subjectentitled “Creating New Drugs Using Intestinal Bacterial Strain Cocktail”(AMED-LEAP Research Program), and obtained the present invention as theresult of the AMED-LEAP Research Program. The disclosure relates tocompositions of bacterial strains and methods for the induction and/orproliferation of CD8+ T-cells by administering these compositions. Thedisclosure also provides compositions and methods for the treatment ofdiseases that can be treated by the induction and/or proliferation ofCD8+ T-cells. Diseases that can be treated by the induction and/orproliferation of CD8+ T-cells include infectious diseases and cancers.

As disclosed herein, for the first-time compositions of human-derivedbacterial strains are provided which activate the immune system throughthe induction of interferon gamma producing CD8+ T cells (also referredto herein as IFNγ+CD8+ T cells, CD8+ IFNγ+ T cells, CD8+ T cells or CD8positive T-cells). While microbial-based compositions for inducingproliferation or accumulation of regulatory T-cells (WO2011/152566), andcomposition for inducing Th17 cells (WO2015/156419) were previouslyreported, this disclosure is the first report on microbial species whichinduce IFNγ+CD8+ T-cells. IFNγ+CD8+ T-cells play important roles in theimmune system, in particular the surveillance of infections (e.g., viralinfections) and cancer cell development. The compositions providedherein can therefore be used in, for instance, the treatment ofinfectious diseases and cancer immunotherapy.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strains ofspecies selected from the group consisting of Phascolarctobacteriumfaecium, Fusobacterium ulcerans, Bacteroides dorei, Bacteroidesuniformis, Subdoligranulum sp., Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes sp., Parabacteroides gordonii,Eubacterum limosum, Parabacteroides distasonis, Bacteroidescellulosilyticus, Bacteroides clarus, Anaerostipes caccae, Bacteroidessalyersiae, Bacteroides fragilis, Bacteroides uniformis, Bacteroideseggerthii, Clostridium sp., Parabacteroides goldsteinii, Bacteroidessp., Lachnospiraceae bacterium HGA0140, Hungatella hathewayi,Clostridium lavalense, Ruminococcus sp., and Clostridium innocuum. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 2, at least 3, at least 4, at least5, at least 6, at least 7, at least 8, at least 9, at least 10, at least11, at least 12, at least 13, at least 14, at least 15, at least 16, atleast 17, at least 18, at least 19, at least 20, at least 21, at least22, at least 23, at least 24, at least 25, or at least 26 bacterialstrains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strains ofspecies selected from the group consisting of Phascolarctobacteriumfaecium, Fusobacterium ulcerans, Bacteroides dorei, Bacteroidesuniformis, Subdoligranulum sp., Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes sp., Parabacteroides gordonii,Eubacterum limosum, Parabacteroides distasonis, Bacteroidescellulosilyticus, Bacteroides clarus, Anaerostipes caccae, Bacteroidessalyersiae, Bacteroides fragilis, Bacteroides uniformis, Bacteroideseggerthii, Clostridium sp., Parabacteroides goldsteinii, Bacteroidessp., Lachnospiraceae bacterium HGA0140, Hungatella hathewayi,Clostridium lavalense, Ruminococcus sp., and Clostridium innocuum. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, at least 7, at least 8, at least 9, at least 10, at least 11, atleast 12, at least 13, at least 14, at least 15, at least 16, at least17, at least 18, at least 19, at least 20, at least 21, at least 22, atleast 23, at least 24, at least 25, or at least 26 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strains ofspecies selected from the group consisting of Phascolarctobacteriumfaecium, Fusobacterium ulcerans, Bacteroides dorei, Bacteroidesuniformis, Subdoligranulum sp., Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes sp., Parabacteroides gordonii,Eubacterum limosum, Parabacteroides distasonis, Bacteroidescellulosilyticus, Bacteroides clarus, Anaerostipes caccae, Bacteroidessalyersiae, Bacteroides fragilis, Bacteroides uniformis, Bacteroideseggerthii, Clostridium sp., Parabacteroides goldsteinii, and Bacteroidessp. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 2, at least 3, at least 4,at least 5, at least 6, at least 7, at least 8, at least 9, at least 10,at least 11, at least 12, at least 13, at least 14, at least 15, atleast 16, at least 17, at least 18, at least 19, at least 20, or atleast 21 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strains ofspecies selected from the group consisting of Phascolarctobacteriumfaecium, Fusobacterium ulcerans, Bacteroides dorei, Bacteroidesuniformis, Subdoligranulum sp., Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes sp., Parabacteroides gordonii,Eubacterum limosum, Parabacteroides distasonis, Bacteroidescellulosilyticus, Bacteroides clarus, Anaerostipes caccae, Bacteroidessalyersiae, Bacteroides fragilis, Bacteroides uniformis, Bacteroideseggerthii, Clostridium sp., Parabacteroides goldsteinii, and Bacteroidessp. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 3, at least 4, at least 5,at least 6, at least 7, at least 8, at least 9, at least 10, at least11, at least 12, at least 13, at least 14, at least 15, at least 16, atleast 17, at least 18, at least 19, at least 20, or at least 21bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strains ofspecies selected from the group consisting of Phascolarctobacteriumfaecium, Fusobacterium ulcerans, Bacteroides dorei, Bacteroidesuniformis, Subdoligranulum sp., Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes sp., Parabacteroides gordonii,Eubacterum limosum, and Parabacteroides distasonis. In some embodimentsof the compositions provided herein, the purified bacterial mixturecomprises at least 2, at least 3, at least 4, at least 5, at least 6, atleast 7, at least 8, at least 9, at least 10, or at least 11 bacterialstrains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising Phascolarctobacterium faecium,Fusobacterium ulcerans, Bacteroides dorei, Bacteroides uniformis,Subdoligranulum sp., Paraprevotella xylaniphila, Parabacteroidesjohnsonii, Alistipes sp., Parabacteroides gordonii, Eubacterum limosum,and Parabacteroides distasonis. In one aspect, the disclosure providescompositions comprising a purified bacterial mixture consisting ofPhascolarctobacterium faecium, Fusobacterium ulcerans, Bacteroidesdorei, Bacteroides uniformis, Subdoligranulum sp., Paraprevotellaxylaniphila, Parabacteroides johnsonii, Alistipes sp., Parabacteroidesgordonii, Eubacterum limosum, and Parabacteroides distasonis.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture essentially consisting ofPhascolarctobacterium faecium, Fusobacterium ulcerans, Bacteroidesdorei, Bacteroides uniformis, Subdoligranulum sp., Paraprevotellaxylaniphila, Parabacteroides johnsonii, Alistipes sp., Parabacteroidesgordonii, Eubacterum limosum, and Parabacteroides distasonis. In oneaspect, the disclosure provides compositions comprising a purifiedbacterial mixture comprising one or more bacterial strains of speciesselected from the group consisting of Phascolarctobacterium faecium,Phascolarctobacterium sp. CAG:207, Fusobacterium ulcerans, Fusobacteriumvarium, Bacteroides dorei, Bacteroides fluxus, Bacteroides uniformis,Bacteroides sp. D20 Subdoligranulum sp., Ruthenibacteriumlactatiformans, Ruminococcaceae bacterium cv2, Gemminger formicilis,Paraprevotella xylaniphila, Parabacteroides johnsonii, Alistipes sp.,Alistipes timonensis, Alistipes senegalesis, Parabacteroides gordonii,Parabacteroides sp. HGS0025, Eubacterum limosum, Parabacteroides sp.CAG:2 and Parabacteroides distasonis. In some embodiments of thecompositions provided herein, the purified bacterial mixture comprisesat least 2, at least 3, at least 4, at least 5, at least 6, at least 7,at least 8, at least 9, at least 10, or at least 11 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising:

1) Phascolarctobacterium faecium, or Phascolarctobacterium sp. CAG:207,

2) Fusobacterium ulcerans, or Fusobacterium varium,

3) Bacteroides dorei, or Bacteroides fluxus,

4) Bacteroides uniformis, or Bacteroides sp. D20,

5) Subdoligranulum sp., Ruthenibacterium lactatiformans, Ruminococcaceaebacterium cv2, or Gemminger formicilis,

6) Paraprevotella xylaniphila,

7) Parabacteroides johnsonii,

8) Alistipes sp., Alistipes timonensis, or Alistipes senegalesis,

9) Parabacteroides gordonii, or Parabacteroides sp. HGS0025,

10) Eubacterum limosum, and

11) Parabacteroides sp. CAG:2 or Parabacteroides distasonis.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture consisting of:

1) Phascolarctobacterium faecium, or Phascolarctobacterium sp. CAG:207,

2) Fusobacterium ulcerans, or Fusobacterium varium,

3) Bacteroides dorei, or Bacteroides fluxus,

4) Bacteroides uniformis, or Bacteroides sp. D20,

5) Subdoligranulum sp., Ruthenibacterium lactatiformans, Ruminococcaceaebacterium cv2, or Gemminger formicilis,

6) Paraprevotella xylaniphila,

7) Parabacteroides johnsonii,

8) Alistipes sp., Alistipes timonensis, or Alistipes senegalesis,

9) Parabacteroides gordonii, or Parabacteroides sp. HGS0025,

10) Eubacterum limosum, and

11) Parabacteroides sp. CAG:2 or Parabacteroides distasonis.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strains ofspecies selected from the group consisting of Phascolarctobacteriumfaecium, Fusobacterium varium, Bacteroides dorei, Bacteroides uniformis,Ruthenibacterium lactatiformans, Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes senegalesis, Parabacteroidesgordonii, Eubacterum limosum, and Parabacteroides distasonis. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 2, at least 3, at least 4, at least 5, atleast 6, at least 7, at least 8, at least 9, at least 10, or at least 11bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising Phascolarctobacterium faecium,Fusobacterium varium, Bacteroides dorei, Bacteroides uniformis,Ruthenibacterium lactatiformans, Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes senegalesis, Parabacteroidesgordonii, Eubacterum limosum, and Parabacteroides distasonis.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture consisting of Phascolarctobacterium faecium,Fusobacterium varium, Bacteroides dorei, Bacteroides uniformis,Ruthenibacterium lactatiformans, Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes senegalesis, Parabacteroidesgordonii, Eubacterum limosum, and Parabacteroides distasonis. In oneaspect, the disclosure provides compositions comprising a purifiedbacterial mixture essentially consisting of Phascolarctobacteriumfaecium, Fusobacterium varium, Bacteroides dorei, Bacteroides uniformis,Ruthenibacterium lactatiformans, Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes senegalesis, Parabacteroidesgordonii, Eubacterum limosum, and Parabacteroides distasonis.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strains ofspecies selected from the group consisting of Phascolarctobacterium sp.CAG:207, Fusobacterium ulcerans, Bacteroides dorei, Bacteroides sp. D20,Ruminococcaceae bacterium cv2, Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes senegalesis, Parabacteroides sp.HGS0025, Eubacterum limosum, and Parabacteroides sp. CAG:2. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 2, at least 3, at least 4, at least 5, atleast 6, at least 7, at least 8, at least 9, at least 10, or at least 11bacterial strains. In one aspect, the disclosure provides compositionscomprising a purified bacterial mixture comprising Phascolarctobacteriumsp. CAG:207, Fusobacterium ulcerans, Bacteroides dorei, Bacteroides sp.D20, Ruminococcaceae bacterium cv2, Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes senegalesis, Parabacteroides sp.HGS0025, Eubacterum limosum, and Parabacteroides sp. CAG:2.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture consisting of Phascolarctobacterium sp.CAG:207, Fusobacterium ulcerans, Bacteroides dorei, Bacteroides sp. D20,Ruminococcaceae bacterium cv2, Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes senegalesis, Parabacteroides sp.HGS0025, Eubacterum limosum, and Parabacteroides sp. CAG:2. In oneaspect, the disclosure provides compositions comprising a purifiedbacterial mixture essentially consisting of Phascolarctobacterium sp.CAG:207, Fusobacterium ulcerans, Bacteroides dorei, Bacteroides sp. D20,Ruminococcaceae bacterium cv2, Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes senegalesis, Parabacteroides sp.HGS0025, Eubacterum limosum, and Parabacteroides sp. CAG:2.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strains ofspecies selected from the group consisting of Phascolarctobacteriumfaecium, Fusobacterium ulcerans, Bacteroides dorei, Bacteroidesuniformis, Subdoligranulum sp., Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes sp., Parabacteroides gordonii,Eubacterum limosum, and Parabacteroides distasonis. In some embodimentsof the compositions provided herein, the purified bacterial mixturecomprises at least 3, at least 4, at least 5, at least 6, at least 7, atleast 8, at least 9, at least 10, or at least 11 bacterial strains. Inone aspect, the disclosure provides compositions comprising a purifiedbacterial mixture comprising two or more bacterial strains of speciesselected from the group consisting of Phascolarctobacterium faecium,Phascolarctobacterium sp. CAG:207, Fusobacterium ulcerans, Fusobacteriumvarium, Bacteroides dorei, Bacteroides fluxus, Bacteroides uniformis,Bacteroides sp. D20 Subdoligranulum sp., Ruthenibacteriumlactatiformans, Ruminococcaceae bacterium cv2, Gemminger formicilis,Paraprevotella xylaniphila, Parabacteroides johnsonii, Alistipes sp.,Alistipes senegalesis, Parabacteroides gordonii, Parabacteroides sp.HGS0025, Eubacterum limosum, Parabacteroides sp. CAG:2 andParabacteroides distasonis. In some embodiments of the compositionsprovided herein, the purified bacterial mixture comprises, at least 3,at least 4, at least 5, at least 6, at least 7, at least 8, at least 9,at least 10, or at least 11 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strains ofspecies selected from the group consisting of Phascolarctobacteriumfaecium, Fusobacterium varium, Bacteroides dorei, Bacteroides uniformis,Ruthenibacterium lactatiformans, Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes senegalesis, Parabacteroidesgordonii, Eubacterum limosum, and Parabacteroides distasonis. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 3, at least 4, at least 5, at least 6, atleast 7, at least 8, at least 9, at least 10, or at least 11 bacterialstrains. In one aspect, the disclosure provides compositions comprisinga purified bacterial mixture comprising two or more bacterial strains ofspecies selected from the group consisting of Phascolarctobacterium sp.CAG:207, Fusobacterium ulcerans, Bacteroides dorei, Bacteroides sp. D20,Ruminococcaceae bacterium cv2, Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes senegalesis, Parabacteroides sp.HGS0025, Eubacterum limosum, and Parabacteroides sp. CAG:2. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 3, at least 4, at least 5, at least 6, atleast 7, at least 8, at least 9, at least 10, or at least 11 bacterialstrains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strains ofspecies selected from the group consisting of Bacteroidescellulosilyticus, Bacteroides clarus, Anaerostipes caccae, Bacteroidessalyersiae, Bacteroides fragilis, Bacteroides uniformis, Bacteroideseggerthii, Clostridium sp., Parabacteroides goldsteinii, Bacteroidessp., Lachnospiraceae bacterium HGA0140, Hungatella hathewayi,Clostridium lavalense, Ruminococcus sp., and Clostridium innocuum. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 2, at least 3, at least 4, at least5, at least 6, at least 7, at least 8, at least 9, at least 10, at least11, at least 12, at least 13, at least 14, or at least 15 bacterialstrains. In one aspect, the disclosure provides compositions comprisinga purified bacterial mixture comprising two or more bacterial strains ofspecies selected from the group consisting of Bacteroidescellulosilyticus, Bacteroides clarus, Anaerostipes caccae, Bacteroidessalyersiae, Bacteroides fragilis, Bacteroides uniformis, Bacteroideseggerthii, Clostridium sp., Parabacteroides goldsteinii, Bacteroidessp., Lachnospiraceae bacterium HGA0140, Hungatella hathewayi,Clostridium lavalense, Ruminococcus sp., and Clostridium innocuum. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, at least 7, at least 8, at least 9, at least 10, at least 11, atleast 12, at least 13, at least 14, or at least 15 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strains ofspecies selected from the group consisting of Bacteroidescellulosilyticus, Bacteroides clarus, Anaerostipes caccae, Bacteroidessalyersiae, Bacteroides fragilis, Bacteroides uniformis, Bacteroideseggerthii, Clostridium sp., Parabacteroides goldsteinii, and Bacteroidessp. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 2, at least 3, at least 4,at least 5, at least 6, at least 7, at least 8, at least 9, or at least10 bacterial strains. In one aspect, the disclosure providescompositions comprising a purified bacterial mixture comprising two ormore bacterial strains of species selected from the group consisting ofBacteroides cellulosilyticus, Bacteroides clarus, Anaerostipes caccae,Bacteroides salyersiae, Bacteroides fragilis, Bacteroides uniformis,Bacteroides eggerthii, Clostridium sp., Parabacteroides goldsteinii, andBacteroides sp. In some embodiments of the compositions provided herein,the purified bacterial mixture comprises at least 3, at least 4, atleast 5, at least 6, at least 7, at least 8, at least 9, or at least 10bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strains ofspecies selected from the group consisting of Phascolarctobacteriumfaecium, Fusobacterium ulcerans, Subdoligranulum sp., and Eubacterumlimosum. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 2, at least 3, or at least4 bacterial strains. In one aspect, the disclosure provides compositionscomprising a purified bacterial mixture comprising two or more bacterialstrains of species selected from the group consisting ofPhascolarctobacterium faecium, Fusobacterium ulcerans, Subdoligranulumsp., and Eubacterum limosum. In some embodiments of the compositionsprovided herein, the purified bacterial mixture comprises at least 3, orat least 4 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strains ofspecies selected from the group consisting of Bacteroides dorei,Bacteroides uniformis, Paraprevotella xylaniphila, Parabacteroidesjohnsonii, Alistipes sp., Parabacteroides gordonii, and Parabacteroidesdistasonis. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 2, at least 3, at least 4,at least 5, at least 6, or at least 7 bacterial strains. In one aspect,the disclosure provides compositions comprising a purified bacterialmixture comprising two or more bacterial strains of species selectedfrom the group consisting of Bacteroides dorei, Bacteroides uniformis,Paraprevotella xylaniphila, Parabacteroides johnsonii, Alistipes sp.,Parabacteroides gordonii, and Parabacteroides distasonis. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 3, at least 4, at least 5, at least 6, or atleast 7 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 95% homology to SEQ ID NO:1,SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ IDNO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ IDNO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ IDNO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ IDNO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, or SEQ ID NO:26. Insome embodiments of the compositions provided herein, the one or morebacterial strain comprises 16S rDNA sequences of at least 96%, at least97%, at least 98%, or at least 99% homology to the SEQ ID NOs. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 2, at least 3, at least 4, at least 5, atleast 6, at least 7, at least 8, at least 9, at least 10, at least 11,at least 12, at least 13, at least 14, at least 15, at least 16, atleast 17, at least 18, at least 19, at least 20, at least 21, at least22, at least 23, at least 24, at least 25, or at least 26 bacterialstrains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 95% sequence identity with SEQID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ IDNO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11,SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16,SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21,SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, or SEQ ID NO:26.In some embodiments of the compositions provided herein, the one or morebacterial strain comprises 16S rDNA sequences of at least 96%, at least97%, at least 98%, or at least 99% sequence identity with the SEQ IDNOs. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 2, at least 3, at least 4,at least 5, at least 6, at least 7, at least 8, at least 9, at least 10,at least 11, at least 12, at least 13, at least 14, at least 15, atleast 16, at least 17, at least 18, at least 19, at least 20, at least21, at least 22, at least 23, at least 24, at least 25, or at least 26bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 95% homology to SEQ ID NO:1,SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ IDNO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ IDNO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ IDNO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ IDNO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, or SEQ ID NO:26. Insome embodiments of the compositions provided herein, the bacterialstrain comprises 16S rDNA sequences of at least 96%, at least 97%, atleast 98%, or at least 99% homology to the SEQ ID NOs. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 3, at least 4, at least 5, at least 6, atleast 7, at least 8, at least 9, at least 10, at least 11, at least 12,at least 13, at least 14, at least 15, at least 16, at least 17, atleast 18, at least 19, at least 20, at least 21, at least 22, at least23, at least 24, at least 25, or at least 26 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 95% sequence identity with SEQID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ IDNO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11,SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16,SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21,SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, or SEQ ID NO:26.In some embodiments of the compositions provided herein, the bacterialstrain comprises 16S rDNA sequences of at least 96%, at least 97%, atleast 98%, or at least 99% sequence identity with the SEQ ID NOs. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, at least 7, at least 8, at least 9, at least 10, at least 11, atleast 12, at least 13, at least 14, at least 15, at least 16, at least17, at least 18, at least 19, at least 20, at least 21, at least 22, atleast 23, at least 24, at least 25, or at least 26 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% homology to SEQ ID NO:1,SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ IDNO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ IDNO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ IDNO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ IDNO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, or SEQ ID NO:26. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, at least 7, at least 8, at least 9, at least 10, at least 11, atleast 12, at least 13, at least 14, at least 15, at least 16, at least17, at least 18, at least 19, at least 20, at least 21, at least 22, atleast 23, at least 24, at least 25, or at least 26 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ IDNO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11,SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16,SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21,SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, or SEQ ID NO:26.In some embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, at least 7, at least 8, at least 9, at least 10, at least 11, atleast 12, at least 13, at least 14, at least 15, at least 16, at least17, at least 18, at least 19, at least 20, at least 21, at least 22, atleast 23, at least 24, at least 25, or at least 26 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 95% homology to SEQ ID NO:1,SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ IDNO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ IDNO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ IDNO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, or SEQ ID NO:21. Insome embodiments of the compositions provided herein, the one or morebacterial strain comprises 16S rDNA sequences of at least 96%, at least97%, at least 98%, or at least 99% homology to the SEQ ID NOs. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 2, at least 3, at least 4, at least 5, atleast 6, at least 7, at least 8, at least 9, at least 10, at least 11,at least 12, at least 13, at least 14, at least 15, at least 16, atleast 17, at least 18, at least 19, at least 20, or at least 21bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 95% sequence identity with SEQID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ IDNO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11,SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16,SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, or SEQ ID NO:21.In some embodiments of the compositions provided herein, the one or morebacterial strain comprises 16S rDNA sequences of at least 96%, at least97%, at least 98%, or at least 99% sequence identity with the SEQ IDNOs. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 2, at least 3, at least 4,at least 5, at least 6, at least 7, at least 8, at least 9, at least 10,at least 11, at least 12, at least 13, at least 14, at least 15, atleast 16, at least 17, at least 18, at least 19, at least 20, or atleast 21 bacterial strains. In one aspect, the disclosure providescompositions comprising a purified bacterial mixture comprising two ormore bacterial strains comprising 16S rDNA sequences of at least 95%homology to SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ IDNO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10,SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15,SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, orSEQ ID NO:21. In some embodiments of the compositions provided herein,the bacterial strain comprises 16S rDNA sequences of at least 96%, atleast 97%, at least 98%, or at least 99% homology to the SEQ ID NOs. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, at least 7, at least 8, at least 9, at least 10, at least 11, atleast 12, at least 13, at least 14, at least 15, at least 16, at least17, at least 18, at least 19, at least 20, or at least 21 bacterialstrains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 95% sequence identity with SEQID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ IDNO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11,SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16,SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, or SEQ ID NO:21.In some embodiments of the compositions provided herein, the bacterialstrain comprises 16S rDNA sequences of at least 96%, at least 97%, atleast 98%, or at least 99% sequence identity with the SEQ ID NOs. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, at least 7, at least 8, at least 9, at least 10, at least 11, atleast 12, at least 13, at least 14, at least 15, at least 16, at least17, at least 18, at least 19, at least 20, or at least 21 bacterialstrains. In one aspect, the disclosure provides compositions comprisinga purified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% homology to SEQ ID NO:1,SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ IDNO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ IDNO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ IDNO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, or SEQ ID NO:21. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, at least 7, at least 8, at least 9, at least 10, at least 11, atleast 12, at least 13, at least 14, at least 15, at least 16, at least17, at least 18, at least 19, at least 20, or at least 21 bacterialstrains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ IDNO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11,SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16,SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, or SEQ ID NO:21.In some embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, at least 7, at least 8, at least 9, at least 10, at least 11, atleast 12, at least 13, at least 14, at least 15, at least 16, at least17, at least 18, at least 19, at least 20, or at least 21 bacterialstrains. In one aspect, the disclosure provides compositions comprisinga purified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 95% homology to SEQ ID NO:1,SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ IDNO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, or SEQ ID NO:11. In someembodiments of the compositions provided herein, the one or morebacterial strain comprises 16S rDNA sequences of at least 96%, at least97%, at least 98%, or at least 99% homology to the SEQ ID NOs. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 2, at least 3, at least 4, at least 5, atleast 6, at least 7, at least 8, at least 9, at least 10, or at least 11bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 95% sequence identity with SEQID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ IDNO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, or SEQ IDNO:11. In some embodiments of the compositions provided herein, the oneor more bacterial strain comprises 16S rDNA sequences of at least 96%,at least 97%, at least 98%, or at least 99% sequence identity with SEQID NOs. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 2, at least 3, at least 4,at least 5, at least 6, at least 7, at least 8, at least 9, at least 10,or at least 11 bacterial strains. In one aspect, the disclosure providescompositions comprising a purified bacterial mixture comprising two ormore bacterial strains comprising 16S rDNA sequences of at least 95%homology to SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ IDNO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10,or SEQ ID NO:11. In some embodiments of the compositions providedherein, the bacterial strain comprises 16S rDNA sequences of at least96%, at least 97%, at least 98%, or at least 99% homology to the SEQ IDNOs. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 3, at least 4, at least 5,at least 6, at least 7, at least 8, at least 9, at least 10, or at least11 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 95% sequence identity with SEQID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ IDNO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, or SEQ IDNO:11. In some embodiments of the compositions provided herein, thebacterial strain comprises 16S rDNA sequences of at least 96%, at least97%, at least 98%, or at least 99% sequence identity with the SEQ IDNOs. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 3, at least 4, at least 5,at least 6, at least 7, at least 8, at least 9, at least 10, or at least11 bacterial strains. In one aspect, the disclosure providescompositions comprising a purified bacterial mixture comprising two ormore bacterial strains comprising 16S rDNA sequences of at least 95%sequence identity with SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ IDNO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ IDNO:62, SEQ ID NO:63, or SEQ ID NO:64. In some embodiments of thecompositions provided herein, the bacterial strain comprises 16S rDNAsequences of at least 96%, at least 97%, at least 98%, or at least 99%sequence identity with the SEQ ID NOs. In some embodiments of thecompositions provided herein, the purified bacterial mixture comprisesat least 3, at least 4, at least 5, at least 6, at least 7, at least 8,at least 9, at least 10, or at least 11 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% homology to SEQ ID NO:1,SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ IDNO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, or SEQ ID NO:11. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 3, at least 4, at least 5, at least 6, atleast 7, at least 8, at least 9, at least 10, or at least 11 bacterialstrains. In one aspect, the disclosure provides compositions comprisinga purified bacterial mixture comprising bacterial strains comprising 16SrDNA sequences of at least 97% homology to SEQ ID NO:1, SEQ ID NO:2, SEQID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ IDNO:8, SEQ ID NO:9, SEQ ID NO:10, and SEQ ID NO:11.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising:

a bacterial strain comprising a 16S rDNA sequence of at least 97%homology to SEQ ID NO:1,

a bacterial strain comprising a 16S rDNA sequence of at least 97%homology to SEQ ID NO:2,

a bacterial strain comprising a 16S rDNA sequence of at least 97%homology to SEQ ID NO:3,

a bacterial strain comprising a 16S rDNA sequence of at least 97%homology to SEQ ID NO:4,

a bacterial strain comprising a 16S rDNA sequence of at least 97%homology to SEQ ID NO:5,

a bacterial strain comprising a 16S rDNA sequence of at least 97%homology to SEQ ID NO:6,

a bacterial strain comprising a 16S rDNA sequence of at least 97%homology to SEQ ID NO:7,

a bacterial strain comprising a 16S rDNA sequence of at least 97%homology to SEQ ID NO:8,

a bacterial strain comprising a 16S rDNA sequence of at least 97%homology to SEQ ID NO:9,

a bacterial strain comprising a 16S rDNA sequence of at least 97%homology to SEQ ID NO:10, and

a bacterial strain comprising a 16S rDNA sequence of at least 97%homology to SEQ ID NO:11.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture consisting of bacterial strains comprising16S rDNA sequences of at least 97% homology to SEQ ID NO:1, SEQ ID NO:2,SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ IDNO:8, SEQ ID NO:9, SEQ ID NO:10, and SEQ ID NO:11.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture consisting of:

a bacterial strain comprising a 16S rDNA sequence of at least 97%homology to SEQ ID NO:1,

a bacterial strain comprising a 16S rDNA sequence of at least 97%homology to SEQ ID NO:2,

a bacterial strain comprising a 16S rDNA sequence of at least 97%homology to SEQ ID NO:3,

a bacterial strain comprising a 16S rDNA sequence of at least 97%homology to SEQ ID NO:4,

a bacterial strain comprising a 16S rDNA sequence of at least 97%homology to SEQ ID NO:5,

a bacterial strain comprising a 16S rDNA sequence of at least 97%homology to SEQ ID NO:6,

a bacterial strain comprising a 16S rDNA sequence of at least 97%homology to SEQ ID NO:7,

a bacterial strain comprising a 16S rDNA sequence of at least 97%homology to SEQ ID NO:8,

a bacterial strain comprising a 16S rDNA sequence of at least 97%homology to SEQ ID NO:9,

a bacterial strain comprising a 16S rDNA sequence of at least 97%homology to SEQ ID NO:10, and

a bacterial strain comprising a 16S rDNA sequence of at least 97%homology to SEQ ID NO:11.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ IDNO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, or SEQ IDNO:11. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 3, at least 4, at least 5,at least 6, at least 7, at least 8, at least 9, at least 10, or at least11 bacterial strains. In one aspect, the disclosure providescompositions comprising a purified bacterial mixture comprising two ormore bacterial strains comprising 16S rDNA sequences of at least 99%sequence identity with SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ IDNO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9,SEQ ID NO:10, or SEQ ID NO:11. In some embodiments of the compositionsprovided herein, the purified bacterial mixture comprises at least 3, atleast 4, at least 5, at least 6, at least 7, at least 8, at least 9, atleast 10, or at least 11 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising bacterial strains comprising 16SrDNA sequences of at least 97% sequence identity with SEQ ID NO:1, SEQID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ IDNO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, and SEQ ID NO:11.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising bacterial strains comprising 16SrDNA sequences of at least 99% sequence identity with SEQ ID NO:1, SEQID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ IDNO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, and SEQ ID NO:11.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising:

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:1,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:2,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:3,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:4,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:5,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:6,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:7,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:8,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:9,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:10, and

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:11.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising:

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:1,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:2,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:3,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:4,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:5,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:6,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:7,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:8,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:9,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:10, and

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:11.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising bacterial strains comprising 16SrDNA sequences with SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4,SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ IDNO:10, and SEQ ID NO:11. In one aspect, the disclosure providescompositions comprising a purified bacterial mixture consisting ofbacterial strains comprising 16S rDNA sequences of at least 97% sequenceidentity with SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ IDNO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10,and SEQ ID NO:11. In one aspect, the disclosure provides compositionscomprising a purified bacterial mixture consisting of bacterial strainscomprising 16S rDNA sequences of at least 99% sequence identity with SEQID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ IDNO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, and SEQ IDNO:11.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture consisting of:

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:1,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:2,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:3,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:4,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:5,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:6,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:7,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:8,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:9,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:10, and

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:11.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture consisting of:

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:1,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:2,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:3,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:4,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:5,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:6,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:7,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:8,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:9,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:10, and

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:11.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture consisting of bacterial strains comprising16S rDNA sequences with SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ IDNO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9,SEQ ID NO:10, and SEQ ID NO:11. In one aspect, the disclosure providescompositions comprising a purified bacterial mixture comprising two ormore bacterial strains comprising 16S rDNA sequences of at least 97%sequence identity with SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ IDNO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ IDNO:62, SEQ ID NO:63, or SEQ ID NO:64. In some embodiments of thecompositions provided herein, the purified bacterial mixture comprisesat least 3, at least 4, at least 5, at least 6, at least 7, at least 8,at least 9, at least 10, or at least 11 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 99% sequence identity with SEQID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ IDNO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, or SEQ IDNO:64. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 3, at least 4, at least 5,at least 6, at least 7, at least 8, at least 9, at least 10, or at least11 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising bacterial strains comprising 16SrDNA sequences of at least 97% sequence identity with SEQ ID NO:54, SEQID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ IDNO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, or SEQ ID NO:64.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising bacterial strains comprising 16SrDNA sequences of at least 99% sequence identity with SEQ ID NO:54, SEQID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ IDNO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, or SEQ ID NO:64.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising:

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:54,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:55,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:56,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:57,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:58,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:59,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:60,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:61,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:62,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:63, and

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:64.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising:

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:54,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:55,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:56,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:57,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:58,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:59,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:60,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:61,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:62,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:63, and

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:64.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising bacterial strains comprising 16SrDNA sequences with SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ IDNO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ IDNO:62, SEQ ID NO:63, or SEQ ID NO:64. In one aspect, the disclosureprovides compositions comprising a purified bacterial mixture consistingof bacterial strains comprising 16S rDNA sequences of at least 97%sequence identity with SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ IDNO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ IDNO:62, SEQ ID NO:63, or SEQ ID NO:64.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture consisting of bacterial strains comprising16S rDNA sequences of at least 99% sequence identity with SEQ ID NO:54,SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59,SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, or SEQ ID NO:64.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture consisting of:

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:54,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:55,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:56,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:57,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:58,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:59,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:60,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:61,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:62,

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:63, and

a bacterial strain comprising a 16S rDNA sequence of at least 97%sequence identity with SEQ ID NO:64.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture consisting of:

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:54,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:55,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:56,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:57,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:58,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:59,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:60,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:61,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:62,

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:63, and

a bacterial strain comprising a 16S rDNA sequence of at least 99%sequence identity with SEQ ID NO:64.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture consisting of bacterial strains comprising16S rDNA sequences with SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ IDNO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ IDNO:62, SEQ ID NO:63, or SEQ ID NO:64.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 95% homology to SEQ ID NO:12,SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17,SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22,SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, or SEQ ID NO:26. In someembodiments of the compositions provided herein, the one or morebacterial strain comprises 16S rDNA sequences of at least 96%, at least97%, at least 98%, or at least 99% homology to the SEQ ID NOs. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 2, at least 3, at least 4, at least 5, atleast 6, at least 7, at least 8, at least 9, at least 10, at least 11,at least 12, at least 13, at least 14, or at least 15 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 95% sequence identity with SEQID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ IDNO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ IDNO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, or SEQ ID NO:26. Insome embodiments of the compositions provided herein, the one or morebacterial strain comprises 16S rDNA sequences of at least 96%, at least97%, at least 98%, or at least 99% sequence identity with the SEQ IDNOs. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 2, at least 3, at least 4,at least 5, at least 6, at least 7, at least 8, at least 9, at least 10,at least 11, at least 12, at least 13, at least 14, or at least 15bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 95% homology to SEQ ID NO:12,SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17,SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22,SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, or SEQ ID NO:26. In someembodiments of the compositions provided herein, the bacterial straincomprises 16S rDNA sequences of at least 96%, at least 97%, at least98%, or at least 99% homology to the SEQ ID NOs. In some embodiments ofthe compositions provided herein, the purified bacterial mixturecomprises at least 3, at least 4, at least 5, at least 6, at least 7, atleast 8, at least 9, at least 10, at least 11, at least 12, at least 13,at least 14, or at least 15 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 95% sequence identity with SEQID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ IDNO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ IDNO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, or SEQ ID NO:26. Insome embodiments of the compositions provided herein, the bacterialstrain comprises 16S rDNA sequences of at least 96%, at least 97%, atleast 98%, or at least 99% sequence identity with the SEQ ID NOs. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, at least 7, at least 8, at least 9, at least 10, at least 11, atleast 12, at least 13, at least 14, or at least 15 bacterial strains. Inone aspect, the disclosure provides compositions comprising a purifiedbacterial mixture comprising two or more bacterial strains comprising16S rDNA sequences of at least 97% homology to SEQ ID NO:12, SEQ IDNO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ IDNO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ IDNO:23, SEQ ID NO:24, SEQ ID NO:25, or SEQ ID NO:26. In some embodimentsof the compositions provided herein, the purified bacterial mixturecomprises at least 3, at least 4, at least 5, at least 6, at least 7, atleast 8, at least 9, at least 10, at least 11, at least 12, at least 13,at least 14, or at least 15 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ IDNO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ IDNO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, or SEQ ID NO:26. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, at least 7, at least 8, at least 9, at least 10, at least 11, atleast 12, at least 13, at least 14, or at least 15 bacterial strains. Inone aspect, the disclosure provides compositions comprising one or morebacterial strains comprising 16S rDNA sequences of at least 95% homologyto SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16,SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, or SEQ ID NO:21.In some embodiments of the compositions provided herein, the one or morebacterial strain comprises 16S rDNA sequences of at least 96%, at least97%, at least 98%, or at least 99% homology to the SEQ ID NOs. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 2, at least 3, at least 4, at least 5, atleast 6, at least 7, at least 8, at least 9, or at least 10 bacterialstrains.

In one aspect, the disclosure provides compositions comprising one ormore bacterial strains comprising 16S rDNA sequences of at least 95%sequence identity with SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ IDNO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ IDNO:20, or SEQ ID NO:21. In some embodiments of the compositions providedherein, the one or more bacterial strain comprises 16S rDNA sequences ofat least 96%, at least 97%, at least 98%, or at least 99% sequenceidentity with the SEQ ID NOs. In some embodiments of the compositionsprovided herein, the purified bacterial mixture comprises at least 2, atleast 3, at least 4, at least 5, at least 6, at least 7, at least 8, atleast 9, or at least 10 bacterial strains. In one aspect, the disclosureprovides compositions comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 95% homology to SEQ ID NO:12,SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17,SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, or SEQ ID NO:21. In someembodiments of the compositions provided herein, the bacterial straincomprises 16S rDNA sequences of at least 96%, at least 97%, at least98%, or at least 99% homology to the SEQ ID NOs. In some embodiments ofthe compositions provided herein, the purified bacterial mixturecomprises at least 3, at least 4, at least 5, at least 6, at least 7, atleast 8, at least 9, or at least 10 bacterial strains.

In one aspect, the disclosure provides compositions comprising two ormore bacterial strains comprising 16S rDNA sequences of at least 95%sequence identity with SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ IDNO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ IDNO:20, or SEQ ID NO:21. In some embodiments of the compositions providedherein, the bacterial strain comprises 16S rDNA sequences of at least96%, at least 97%, at least 98%, or at least 99% sequence identity withthe SEQ ID NOs. In some embodiments of the compositions provided herein,the purified bacterial mixture comprises at least 3, at least 4, atleast 5, at least 6, at least 7, at least 8, at least 9, or at least 10bacterial strains. In one aspect, the disclosure provides compositionscomprising two or more bacterial strains comprising 16S rDNA sequencesof at least 97% homology to SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14,SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19,SEQ ID NO:20, or SEQ ID NO:21. In some embodiments of the compositionsprovided herein, the purified bacterial mixture comprises at least 3, atleast 4, at least 5, at least 6, at least 7, at least 8, at least 9, orat least 10 bacterial strains.

In one aspect, the disclosure provides compositions comprising two ormore bacterial strains comprising 16S rDNA sequences of at least 97%sequence identity with SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ IDNO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ IDNO:20, or SEQ ID NO:21. In some embodiments of the compositions providedherein, the purified bacterial mixture comprises at least 3, at least 4,at least 5, at least 6, at least 7, at least 8, at least 9, or at least10 bacterial strains. In one aspect, the disclosure providescompositions comprising a purified bacterial mixture comprising one ormore bacterial strains comprising 16S rDNA sequences of at least 95%homology to SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:5, or SEQ ID NO:10.

In some embodiments of the compositions provided herein, the one or morebacterial strain comprises 16S rDNA sequences of at least 96%, at least97%, at least 98%, or at least 99% homology to the SEQ ID NOs. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 2, at least 3, or at least 4 bacterialstrains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 95% sequence identity with SEQID NO:1, SEQ ID NO:2, SEQ ID NO:5, or SEQ ID NO:10. In some embodimentsof the compositions provided herein, the one or more bacterial straincomprises 16S rDNA sequences of at least 96%, at least 97%, at least98%, or at least 99% sequence identity with the SEQ ID NOs. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 2, at least 3, or at least 4 bacterialstrains. In one aspect, the disclosure provides compositions comprisinga purified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 95% homology to SEQ ID NO:1,SEQ ID NO:2, SEQ ID NO:5, or SEQ ID NO:10. In some embodiments of thecompositions provided herein, the bacterial strain comprises 16S rDNAsequences of at least 96%, at least 97%, at least 98%, or at least 99%homology to the SEQ ID NOs. In some embodiments of the compositionsprovided herein, the purified bacterial mixture comprises at least 3, orat least 4 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 95% sequence identity with SEQID NO:1, SEQ ID NO:2, SEQ ID NO:5, or SEQ ID NO:10. In some embodimentsof the compositions provided herein, the bacterial strain comprises 16SrDNA sequences of at least 96%, at least 97%, at least 98%, or at least99% sequence identity with the SEQ ID NOs. In some embodiments of thecompositions provided herein, the purified bacterial mixture comprisesat least 3, or at least 4 bacterial strains. In one aspect, thedisclosure provides compositions comprising a purified bacterial mixturecomprising two or more bacterial strains comprising 16S rDNA sequencesof at least 97% homology to SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:5, orSEQ ID NO:10. In some embodiments of the compositions provided herein,the purified bacterial mixture comprises at least 3, or at least 4bacterial strains. In one aspect, the disclosure provides compositionscomprising a purified bacterial mixture comprising two or more bacterialstrains comprising 16S rDNA sequences of at least 97% sequence identitywith the SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:5, or SEQ ID NO:10. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 3, or at least 4 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 95% homology to SEQ ID NO:3,SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, or SEQID NO:11. In some embodiments of the compositions provided herein, theone or more bacterial strain comprises 16S rDNA sequences of at least96%, at least 97%, at least 98%, or at least 99% homology to the SEQ IDNOs. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 2, at least 3, at least 4,at least 5, at least 6, or at least 7 bacterial strains. In one aspect,the disclosure provides compositions comprising a purified bacterialmixture comprising one or more bacterial strains comprising 16S rDNAsequences of at least 95% sequence identity with SEQ ID NO:3, SEQ IDNO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, or SEQ IDNO:11. In some embodiments of the compositions provided herein, the oneor more bacterial strain comprises 16S rDNA sequences of at least 96%,at least 97%, at least 98%, or at least 99% sequence identity with theSEQ ID NOs. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 2, at least 3, at least 4,at least 5, at least 6, or at least 7 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 95% homology to SEQ ID NO:3,SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, or SEQID NO:11. In some embodiments of the compositions provided herein, thebacterial strain comprises 16S rDNA sequences of at least 96%, at least97%, at least 98%, or at least 99% homology to the SEQ ID NOs. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 3, at least 4, at least 5, at least 6, or atleast 7 bacterial strains. In one aspect, the disclosure providescompositions comprising a purified bacterial mixture comprising two ormore bacterial strains comprising 16S rDNA sequences of at least 95%sequence identity with SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ IDNO:7, SEQ ID NO:8, SEQ ID NO:9, or SEQ ID NO:11. In some embodiments ofthe compositions provided herein, the bacterial strain comprises 16SrDNA sequences of at least 96%, at least 97%, at least 98%, or at least99% sequence identity with the SEQ ID NOs. In some embodiments of thecompositions provided herein, the purified bacterial mixture comprisesat least 3, at least 4, at least 5, at least 6, or at least 7 bacterialstrains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% homology to SEQ ID NO:3,SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, or SEQID NO:11. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 3, at least 4, at least 5,at least 6, or at least 7 bacterial strains. In one aspect, thedisclosure provides compositions comprising a purified bacterial mixturecomprising two or more bacterial strains comprising 16S rDNA sequencesof at least 97% sequence identity with SEQ ID NO:3, SEQ ID NO:4, SEQ IDNO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, or SEQ ID NO:11. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 3, at least 4, at least 5, at least 6, or atleast 7 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 95% homology to SEQ ID NO:27,SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32,SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37,SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42,SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47,SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.In some embodiments of the compositions provided herein, the one or morebacterial strain comprises 16S rDNA sequences of at least 96%, at least97%, at least 98%, or at least 99% homology to the SEQ ID NOs. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 2, at least 3, at least 4, at least 5, atleast 6, at least 7, at least 8, at least 9, at least 10, at least 11,at least 12, at least 13, at least 14, at least 15, at least 16, atleast 17, at least 18, at least 19, at least 20, at least 21, at least22, at least 23, at least 24, at least 25, or at least 26 bacterialstrains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 95% sequence identity with SEQID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ IDNO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ IDNO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ IDNO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ IDNO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ IDNO:52. In some embodiments of the compositions provided herein, the oneor more bacterial strain comprises 16S rDNA sequences of at least 96%,at least 97%, at least 98%, or at least 99% sequence identity with theSEQ ID NOs. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 2, at least 3, at least 4,at least 5, at least 6, at least 7, at least 8, at least 9, at least 10,at least 11, at least 12, at least 13, at least 14, at least 15, atleast 16, at least 17, at least 18, at least 19, at least 20, at least21, at least 22, at least 23, at least 24, at least 25, or at least 26bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 95% homology to SEQ ID NO:27,SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32,SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37,SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42,SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47,SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.In some embodiments of the compositions provided herein, the bacterialstrain comprises 16S rDNA sequences of at least 96%, at least 97%, atleast 98%, or at least 99% homology to the SEQ ID NOs. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 3, at least 4, at least 5, at least 6, atleast 7, at least 8, at least 9, at least 10, at least 11, at least 12,at least 13, at least 14, at least 15, at least 16, at least 17, atleast 18, at least 19, at least 20, at least 21, at least 22, at least23, at least 24, at least 25, or at least 26 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 95% sequence identity with SEQID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ IDNO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ IDNO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ IDNO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ IDNO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ IDNO:52. In some embodiments of the compositions provided herein, thebacterial strain comprises 16S rDNA sequences of at least 96%, at least97%, at least 98%, or at least 99% sequence identity with the SEQ IDNOs. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 3, at least 4, at least 5,at least 6, at least 7, at least 8, at least 9, at least 10, at least11, at least 12, at least 13, at least 14, at least 15, at least 16, atleast 17, at least 18, at least 19, at least 20, at least 21, at least22, at least 23, at least 24, at least 25, or at least 26 bacterialstrains. In one aspect, the disclosure provides compositions comprisinga purified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% homology to SEQ ID NO:27,SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32,SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37,SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42,SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47,SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.In some embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, at least 7, at least 8, at least 9, at least 10, at least 11, atleast 12, at least 13, at least 14, at least 15, at least 16, at least17, at least 18, at least 19, at least 20, at least 21, at least 22, atleast 23, at least 24, at least 25, or at least 26 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ IDNO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ IDNO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ IDNO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ IDNO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ IDNO:52. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 3, at least 4, at least 5,at least 6, at least 7, at least 8, at least 9, at least 10, at least11, at least 12, at least 13, at least 14, at least 15, at least 16, atleast 17, at least 18, at least 19, at least 20, at least 21, at least22, at least 23, at least 24, at least 25, or at least 26 bacterialstrains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 95% homology to SEQ ID NO:27,SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32,SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37,SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42,SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, and SEQ IDNO:47. In some embodiments of the compositions provided herein, the oneor more bacterial strain comprises 16S rDNA sequences of at least 96%,at least 97%, at least 98%, or at least 99% homology to the SEQ ID NOs.In some embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 2, at least 3, at least 4, at least5, at least 6, at least 7, at least 8, at least 9, at least 10, at least11, at least 12, at least 13, at least 14, at least 15, at least 16, atleast 17, at least 18, at least 19, at least 20, or at least 21bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 95% sequence identity with SEQID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ IDNO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ IDNO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ IDNO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, and SEQID NO:47. In some embodiments of the compositions provided herein, theone or more bacterial strain comprises 16S rDNA sequences of at least96%, at least 97%, at least 98%, or at least 99% sequence identity withthe SEQ ID NOs. In some embodiments of the compositions provided herein,the purified bacterial mixture comprises at least 2, at least 3, atleast 4, at least 5, at least 6, at least 7, at least 8, at least 9, atleast 10, at least 11, at least 12, at least 13, at least 14, at least15, at least 16, at least 17, at least 18, at least 19, at least 20, orat least 21 bacterial strains. In one aspect, the disclosure providescompositions comprising a purified bacterial mixture comprising two ormore bacterial strains comprising 16S rDNA sequences of at least 95%homology to SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ IDNO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ IDNO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ IDNO:46, and SEQ ID NO:47. In some embodiments of the compositionsprovided herein, the bacterial strain comprises 16S rDNA sequences of atleast 96%, at least 97%, at least 98%, or at least 99% homology to theSEQ ID NOs. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 3, at least 4, at least 5,at least 6, at least 7, at least 8, at least 9, at least 10, at least11, at least 12, at least 13, at least 14, at least 15, at least 16, atleast 17, at least 18, at least 19, at least 20, or at least 21bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 95% sequence identity with SEQID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ IDNO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ IDNO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ IDNO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, and SEQID NO:47. In some embodiments of the compositions provided herein, thebacterial strain comprises 16S rDNA sequences of at least 96%, at least97%, at least 98%, or at least 99% sequence identity with the SEQ IDNOs. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 3, at least 4, at least 5,at least 6, at least 7, at least 8, at least 9, at least 10, at least11, at least 12, at least 13, at least 14, at least 15, at least 16, atleast 17, at least 18, at least 19, at least 20, or at least 21bacterial strains. In one aspect, the disclosure provides compositionscomprising a purified bacterial mixture comprising two or more bacterialstrains comprising 16S rDNA sequences of at least 97% homology to SEQ IDNO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ IDNO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ IDNO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ IDNO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, and SEQID NO:47. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 3, at least 4, at least 5,at least 6, at least 7, at least 8, at least 9, at least 10, at least11, at least 12, at least 13, at least 14, at least 15, at least 16, atleast 17, at least 18, at least 19, at least 20, or at least 21bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ IDNO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ IDNO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ IDNO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, and SEQID NO:47. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 3, at least 4, at least 5,at least 6, at least 7, at least 8, at least 9, at least 10, at least11, at least 12, at least 13, at least 14, at least 15, at least 16, atleast 17, at least 18, at least 19, at least 20, or at least 21bacterial strains. In one aspect, the disclosure provides compositionscomprising a purified bacterial mixture comprising one or more bacterialstrains comprising 16S rDNA sequences of at least 95% homology to SEQ IDNO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ IDNO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, or SEQ IDNO:37. In some embodiments of the compositions provided herein, the oneor more bacterial strain comprises 16S rDNA sequences of at least 96%,at least 97%, at least 98%, or at least 99% homology to the SEQ ID NOs.In some embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 2, at least 3, at least 4, at least5, at least 6, at least 7, at least 8, at least 9, at least 10, or atleast 11 bacterial strains. In one aspect, the disclosure providescompositions comprising a purified bacterial mixture comprising one ormore bacterial strains comprising 16S rDNA sequences of at least 95%sequence identity with SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ IDNO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ IDNO:35, SEQ ID NO:36, or SEQ ID NO:37. In some embodiments of thecompositions provided herein, the one or more bacterial strain comprises16S rDNA sequences of at least 96%, at least 97%, at least 98%, or atleast 99% sequence identify with the SEQ ID NOs. In some embodiments ofthe compositions provided herein, the purified bacterial mixturecomprises at least 2, at least 3, at least 4, at least 5, at least 6, atleast 7, at least 8, at least 9, at least 10, or at least 11 bacterialstrains. In one aspect, the disclosure provides compositions comprisinga purified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 95% homology to SEQ ID NO:27,SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32,SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, or SEQ ID NO:37.In some embodiments of the compositions provided herein, the bacterialstrain comprises 16S rDNA sequences of at least 96%, at least 97%, atleast 98%, or at least 99% homology to the SEQ ID NOs. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 3, at least 4, at least 5, at least 6, atleast 7, at least 8, at least 9, at least 10, or at least 11 bacterialstrains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 95% sequence identity with SEQID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ IDNO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, or SEQ IDNO:37. In some embodiments of the compositions provided herein, thebacterial strain comprises 16S rDNA sequences of at least 96%, at least97%, at least 98%, or at least 99% sequence identity with the SEQ IDNOs. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 3, at least 4, at least 5,at least 6, at least 7, at least 8, at least 9, at least 10, or at least11 bacterial strains. In one aspect, the disclosure providescompositions comprising a purified bacterial mixture comprising two ormore bacterial strains comprising 16S rDNA sequences of at least 97%homology to SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ IDNO:36, or SEQ ID NO:37. In some embodiments of the compositions providedherein, the purified bacterial mixture comprises at least 3, at least 4,at least 5, at least 6, at least 7, at least 8, at least 9, at least 10,or at least 11 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ IDNO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, or SEQ IDNO:37. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 3, at least 4, at least 5,at least 6, at least 7, at least 8, at least 9, at least 10, or at least11 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 95% homology to SEQ ID NO:38,SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43,SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48,SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52. In someembodiments of the compositions provided herein, the one or morebacterial strain comprises 16S rDNA sequences of at least 96%, at least97%, at least 98%, or at least 99% homology to the SEQ ID NOs. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 2, at least 3, at least 4, at least 5, atleast 6, at least 7, at least 8, at least 9, at least 10, at least 11,at least 12, at least 13, at least 14, or at least 15 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 95% sequence identity with SEQID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ IDNO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ IDNO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52. Insome embodiments of the compositions provided herein, the one or morebacterial strain comprises 16S rDNA sequences of at least 96%, at least97%, at least 98%, or at least 99% sequence identity with the SEQ IDNOs. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 2, at least 3, at least 4,at least 5, at least 6, at least 7, at least 8, at least 9, at least 10,at least 11, at least 12, at least 13, at least 14, or at least 15bacterial strains. In one aspect, the disclosure provides compositionscomprising a purified bacterial mixture comprising two or more bacterialstrains comprising 16S rDNA sequences of at least 95% homology to SEQ IDNO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ IDNO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ IDNO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52. Insome embodiments of the compositions provided herein, the bacterialstrain comprises 16S rDNA sequences of at least 96%, at least 97%, atleast 98%, or at least 99% homology to the SEQ ID NOs. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 3, at least 4, at least 5, at least 6, atleast 7, at least 8, at least 9, at least 10, at least 11, at least 12,at least 13, at least 14, or at least 15 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 95% sequence identity with SEQID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ IDNO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ IDNO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52. Insome embodiments of the compositions provided herein, the bacterialstrain comprises 16S rDNA sequences of at least 96%, at least 97%, atleast 98%, or at least 99% sequence identity with the SEQ ID NOs. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, at least 7, at least 8, at least 9, at least 10, at least 11, atleast 12, at least 13, at least 14, or at least 15 bacterial strains. Inone aspect, the disclosure provides compositions comprising a purifiedbacterial mixture comprising two or more bacterial strains comprising16S rDNA sequences of at least 95% homology to SEQ ID NO:38, SEQ IDNO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ IDNO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ IDNO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52. In some embodimentsof the compositions provided herein, the purified bacterial mixturecomprises at least 3, at least 4, at least 5, at least 6, at least 7, atleast 8, at least 9, at least 10, at least 11, at least 12, at least 13,at least 14, or at least 15 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 95% sequence identity with SEQID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ IDNO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ IDNO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, at least 7, at least 8, at least 9, at least 10, at least 11, atleast 12, at least 13, at least 14, or at least 15 bacterial strains. Inone aspect, the disclosure provides compositions comprising a purifiedbacterial mixture comprising one or more bacterial strains comprising16S rDNA sequences of at least 97% homology to SEQ ID NO:38, SEQ IDNO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ IDNO:44, SEQ ID NO:45, SEQ ID NO:46, or SEQ ID NO:47. In some embodimentsof the compositions provided herein, the one or more bacterial straincomprises 16S rDNA sequences of at least 96%, at least 97%, at least98%, or at least 99% homology to the SEQ ID NOs. In some embodiments ofthe compositions provided herein, the purified bacterial mixturecomprises at least 2, at least 3, at least 4, at least 5, at least 6, atleast 7, at least 8, at least 9, or at least 10 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ IDNO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, or SEQ ID NO:47. Insome embodiments of the compositions provided herein, the one or morebacterial strain comprises 16S rDNA sequences of at least 96%, at least97%, at least 98%, or at least 99% sequence identity with the SEQ IDNOs. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 2, at least 3, at least 4,at least 5, at least 6, at least 7, at least 8, at least 9, or at least10 bacterial strains. In one aspect, the disclosure providescompositions comprising a purified bacterial mixture comprising two ormore bacterial strains comprising 16S rDNA sequences of at least 95%homology to SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, or SEQID NO:47. In some embodiments of the compositions provided herein, thebacterial strain comprises 16S rDNA sequences of at least 96%, at least97%, at least 98%, or at least 99% homology to the SEQ ID NOs. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 3, at least 4, at least 5, at least 6, atleast 7, at least 8, at least 9, or at least 10 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 95% sequence identity with SEQID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ IDNO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, or SEQ ID NO:47. Insome embodiments of the compositions provided herein, the bacterialstrain comprises 16S rDNA sequences of at least 96%, at least 97%, atleast 98%, or at least 99% sequence identity with the SEQ ID NOs. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, at least 7, at least 8, at least 9, or at least 10 bacterial strains.In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% homology to SEQ ID NO:38,SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43,SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, or SEQ ID NO:47. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 3, at least 4, at least 5, at least 6, atleast 7, at least 8, at least 9, or at least 10 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ IDNO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, or SEQ ID NO:47. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, at least 7, at least 8, at least 9, or at least 10 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 95% homology to SEQ ID NO:27,SEQ ID NO:28, SEQ ID NO:31 or SEQ ID NO:36. In some embodiments of thecompositions provided herein, the one or more bacterial strain comprises16S rDNA sequences of at least 96%, at least 97%, at least 98%, or atleast 99% homology to the SEQ ID NOs. In some embodiments of thecompositions provided herein, the purified bacterial mixture comprisesat least 2, at least 3, or at least 4 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 95% sequence identity with SEQID NO:27, SEQ ID NO:28, SEQ ID NO:31 or SEQ ID NO:36. In someembodiments of the compositions provided herein, the one or morebacterial strain comprises 16S rDNA sequences of at least 96%, at least97%, at least 98%, or at least 99% sequence identity with the SEQ IDNOs. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 2, at least 3, or at least4 bacterial strains. In one aspect, the disclosure provides compositionscomprising a purified bacterial mixture comprising two or more bacterialstrains comprising 16S rDNA sequences of at least 95% homology to SEQ IDNO:27, SEQ ID NO:28, SEQ ID NO:31 or SEQ ID NO:36. In some embodimentsof the compositions provided herein, the bacterial strain comprises 16SrDNA sequences of at least 96%, at least 97%, at least 98%, or at least99% homology to the SEQ ID NOs. In some embodiments of the compositionsprovided herein, the purified bacterial mixture comprises at least 3, orat least 4 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 95% sequence identity with SEQID NO:27, SEQ ID NO:28, SEQ ID NO:31 or SEQ ID NO:36. In someembodiments of the compositions provided herein, the bacterial straincomprises 16S rDNA sequences of at least 96%, at least 97%, at least98%, or at least 99% sequence identity with the SEQ ID NOs. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 3, or at least 4 bacterial strains. In oneaspect, the disclosure provides compositions comprising a purifiedbacterial mixture comprising two or more bacterial strains comprising16S rDNA sequences of at least 97% homology to SEQ ID NO:27, SEQ IDNO:28, SEQ ID NO:31 or SEQ ID NO:36. In some embodiments of thecompositions provided herein, the purified bacterial mixture comprisesat least 3, or at least 4 bacterial strains. In one aspect, thedisclosure provides compositions comprising a purified bacterial mixturecomprising two or more bacterial strains comprising 16S rDNA sequencesof at least 97% sequence identity with SEQ ID NO:27, SEQ ID NO:28, SEQID NO:31 or SEQ ID NO:36. In some embodiments of the compositionsprovided herein, the purified bacterial mixture comprises at least 3, orat least 4 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 95% homology to SEQ ID NO:29,SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, orSEQ ID NO:37. In some embodiments of the compositions provided herein,the one or more bacterial strain comprises 16S rDNA sequences of atleast 96%, at least 97%, at least 98%, or at least 99% homology to theSEQ ID NOs. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 2, at least 3, at least 4,at least 5, at least 6, or at least 7 bacterial strains. In one aspect,the disclosure provides compositions comprising a purified bacterialmixture comprising one or more bacterial strains comprising 16S rDNAsequences of at least 95% sequence identity with SEQ ID NO:29, SEQ IDNO:30, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, or SEQ IDNO:37. In some embodiments of the compositions provided herein, the oneor more bacterial strain comprises 16S rDNA sequences of at least 96%,at least 97%, at least 98%, or at least 99% sequence identity with theSEQ ID NOs. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 2, at least 3, at least 4,at least 5, at least 6, or at least 7 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 95% homology to SEQ ID NO:29,SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, orSEQ ID NO:37. In some embodiments of the compositions provided herein,the bacterial strain comprises 16S rDNA sequences of at least 96%, atleast 97%, at least 98%, or at least 99% homology to the SEQ ID NOs. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, or at least 7 bacterial strains. In one aspect, the disclosureprovides compositions comprising a purified bacterial mixture comprisingtwo or more bacterial strains comprising 16S rDNA sequences of at least95% sequence identity with SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:32, SEQID NO:33, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:37. In someembodiments of the compositions provided herein, the bacterial straincomprises 16S rDNA sequences of at least 96%, at least 97%, at least98%, or at least 99% sequence identity with the SEQ ID NOs. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 3, at least 4, at least 5, at least 6, or atleast 7 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% homology to SEQ ID NO:29,SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, orSEQ ID NO:37. In some embodiments of the compositions provided herein,the purified bacterial mixture comprises at least 3, at least 4, atleast 5, at least 6, or at least 7 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:29, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ IDNO:35, or SEQ ID NO:37. In some embodiments of the compositions providedherein, the purified bacterial mixture comprises at least 3, at least 4,at least 5, at least 6, or at least 7 bacterial strains. In someembodiments of the compositions provided herein, at least 50% of thebacterial strains belong to the order of Bacteriodales. In someembodiments of the compositions provided herein, one or more of thebacterial strains belong to the order of Bacteriodales and one or moreof the bacterial strains belong to the order of Clostridiales. In someembodiments of the compositions provided herein, at least 25% of thebacterial strains belong to the family of Bacteroidaceae. In someembodiments of the compositions provided herein, one or more of thebacterial strains belongs to the genus Bacteroides. In some embodimentsof the compositions provided herein, the composition does not includebacterial strains that belong to the order of Bacteriodales. In someembodiments of the compositions provided herein, one or more of thebacterial strains is a spore-former. In some embodiments of thecompositions provided herein, one or more of the bacterial strains is inspore form. In some embodiments of the compositions provided herein, oneor more of the bacterial strains is a non-spore former. In someembodiments of the compositions provided herein, the compositioncomprises only obligate anaerobic bacterial strains. In some embodimentsof the compositions provided herein, one or more of the bacterialstrains does not have an antibiotic resistance gene. In some embodimentsof the compositions provided herein, the antibiotic resistance generenders the bacterial strain resistant to vancomycin. In someembodiments of the compositions provided herein, the bacterial strainsare human-derived bacteria. In some embodiments of the compositionsprovided herein, the bacterial strains are derived from more than onehuman donor. In some embodiments of the compositions provided herein,the composition induces proliferation and/or accumulation ofCD8+T-cells.

In some embodiments of the compositions provided herein, the compositionis a pharmaceutical composition. In some embodiments of thepharmaceutical compositions provided herein, the pharmaceuticalcomposition comprises a pharmaceutically acceptable excipient. In someembodiments of the pharmaceutical compositions provided herein, thepharmaceutical composition is formulated for oral administration. Insome embodiments of the pharmaceutical compositions provided herein, thepharmaceutical composition is formulated for rectal administration. Insome embodiments of the pharmaceutical compositions provided herein, thepharmaceutical composition is formulated for delivery to the intestine.In some embodiments of the pharmaceutical compositions provided herein,the pharmaceutical composition is formulated for delivery to the colon.In some embodiments of the pharmaceutical compositions provided herein,one or more of the bacterial strains is lyophilized. In some embodimentsof the pharmaceutical compositions provided herein, the pharmaceuticalcomposition is in the form of a capsule. In some embodiments of thepharmaceutical compositions provided herein, the pharmaceuticalcomposition further comprises a pH sensitive composition comprising oneor more enteric polymers. In one aspect, the disclosure provides a foodproduct comprising any of the compositions provided herein and anutrient.

In some embodiments of the compositions provided herein, the compositionfurther comprises one or more anticancer agents. In some embodiments ofthe compositions provided herein, the anticancer agent is a chemotherapyagent. In some embodiments of the compositions provided herein, theanticancer agent is cancer immunotherapy agent. In some embodiments ofthe compositions provided herein, the cancer immunotherapy agent is animmune checkpoint inhibitor. In some embodiments of the compositionsprovided herein, the immune checkpoint inhibitor is a PD-1 inhibitor,PD-L-1 inhibitor, or CTLA-4 inhibitor. In some embodiments of thecompositions provided herein, the immune checkpoint inhibitor is a PD-1inhibitor. In some embodiments of the compositions provided herein, theimmune checkpoint inhibitor is a CTLA-4 inhibitor. In some embodimentsof the compositions provided herein, the composition further comprisesone or more cytokines. In some embodiments of the compositions providedherein, the cytokine is IL-2, IL-15, or IL-21. In some embodiments ofthe compositions provided herein, the composition further comprises oneor more costimulatory agents. In some embodiments of the compositionsprovided herein, the costimulatory agent is a CD-28, OX-40, 4-1BB, orCD40 antibody. In some embodiments of the compositions provided herein,the composition further comprises one or more vaccines. In someembodiments of the compositions provided herein, the vaccine is adendritic cell vaccine. In some embodiments of the compositions providedherein, the composition is combined with adoptive cell transfer therapy.In some embodiments of the compositions provided herein, the adoptivecell transfer therapy is the use of engineered T-cell receptors orchimeric antigen receptors.

In one aspect, the disclosure provides a vaccine comprising any of thecompositions provided herein and an antigen. In some embodiments of thevaccines provided herein, the antigen is an HIV antigen. In someembodiments of the vaccines provided herein, the antigen is a hepatitisantigen. In some embodiments of the compositions provided herein, thecomposition further comprises one or more anti-inflammatory agents. Insome embodiments of the compositions provided herein, theanti-inflammatory agent is an NSAID.

In some embodiments of the compositions provided herein, administrationof the composition to a subject results in the induction ofproliferation and/or accumulation of CD8+ T-cells in the intestine ofthe subject. In some embodiments of the compositions provided herein,administration of the composition to a subject results in an increase inIFNγ production in the intestine of a subject. In some embodiments ofthe compositions provided herein, administration of the composition to asubject results in the presence of one or more bacterial strains of theadministered composition in the intestine of the subject. In someembodiments of the compositions provided herein, the one or morebacterial strains of the administered composition was not previouslypresent in the intestine of the subject. In some embodiments of thecompositions provided herein, administration of the composition to asubject results in the engraftment of one or more bacterial strains ofthe administered composition in the intestine of the subject. In someembodiments of the compositions provided herein, the one or morebacterial strains of the administered composition was not previouslyengrafted in the intestine of the subject. In some embodiments of thecompositions provided herein, administration of the composition to asubject results in an increase in the number of the bacterial strains ofthe administered composition in the intestine of the subject. In someembodiments of the compositions provided herein, administration of thecomposition to a subject results in an increase in the number of thebacterial strains of the administered composition engrafted in theintestine of the subject. In some embodiments of the compositionsprovided herein, administration of the composition to a subject resultsin an increase in the amount of bacteria of the bacterial strains of theadministered composition in the intestine of the subject. In someembodiments of the compositions provided herein, administration of thecomposition to a subject results in an increase in the amount ofbacteria of the bacterial strains of the administered compositionengrafted in the intestine of the subject.

In one aspect, the disclosure provides a method of treating a disease ina subject comprising administering any of the compositions providedherein to the subject in an effective amount to treat the disease. Insome embodiments of the methods provided herein, the administration ofthe composition to the subject results in the induction of proliferationand/or accumulation of CD8+ T-cells in the intestine of the subject. Insome embodiments of the methods provided herein, the proliferationand/or accumulation of CD8+ T-cells in the intestine of the subject isincreased by at least 10%, at least 20%, at least 30%, at least 40%, atleast 50%, at least 100%, or at least 200% when compared to theproliferation and/or accumulation of CD8+ T-cells in the intestine ofthe subject before the administration of the composition. In someembodiments of the methods provided herein, the administration of thecomposition to the subject results in an increase of IFNγ production inthe intestine of the subject when compared to the IFNγ production in theintestine of the subject before the administration of the composition.In some embodiments of the methods provided herein, the administrationof the composition to the subject results in an increase of IFNγproduction in the intestine of the subject by at least 10%, at least20%, at least 30%, at least 40%, at least 50%, at least 100%, or atleast 200% when compared to the IFNγ production in the intestine of thesubject before the administration of the composition.

In some embodiments of the methods provided herein, the subject hascancer. In some embodiments of the methods provided herein, the canceris carcinoma, glioma, mesothelioma, melanoma, lymphoma, leukemia,adenocarcinoma, breast cancer, ovarian cancer, cervical cancer,glioblastoma, multiple myeloma, prostate cancer, Burkitt's lymphoma,head and neck cancer, colon cancer, colorectal cancer, non-small celllung cancer, small cell lung cancer, cancer of the esophagus, stomachcancer, pancreatic cancer, hepatobiliary cancer, cancer of thegallbladder, cancer of the small intestine, rectal cancer, kidneycancer, bladder cancer, prostate cancer, penile cancer, urethral cancer,testicular cancer, vaginal cancer, uterine cancer, thyroid cancer,parathyroid cancer, adrenal cancer, pancreatic endocrine cancer,carcinoid cancer, bone cancer, skin cancer, retinoblastomas, Hodgkin'slymphoma, non-Hodgkin's lymphoma, Kaposi's sarcoma, multicentricCastleman's disease, AIDS-associated primary effusion lymphoma,neuroectodermal tumors, or rhabdomyosarcoma. In some embodiments of themethods provided herein, the cancer is prostate cancer, bladder cancer,non-small cell lung cancer, urothelial carcinoma, melanoma, or renalcell carcinoma. In some embodiments of the methods provided herein, thesubject is undergoing radiation treatment.

In some embodiments of the methods provided herein, the method furtherincludes administering one or more anticancer agents. In someembodiments of the methods provided herein, the anticancer agent is achemotherapy agent. In some embodiments of the methods provided herein,the anticancer agent is a cancer immunotherapy agent. In someembodiments of the methods provided herein, the cancer immunotherapyagent is an immune checkpoint inhibitor. In some embodiments of themethods provided herein, the immune checkpoint inhibitor is a PD-1inhibitor, PD-L-1 inhibitor, or CTLA-4 inhibitor. In some embodiments ofthe methods provided herein, the immune checkpoint inhibitor is a PD-1inhibitor. In some embodiments of the methods provided herein, theimmune checkpoint inhibitor is a CTLA-4 inhibitor. In some embodimentsof the methods provided herein, the method further includesadministering one or more cytokines. In some embodiments of the methodsprovided herein the cytokine is IL-2, IL-15, or IL-21.

In some embodiments of the methods provided herein, the method furtherincludes administering one or more costimulatory agents. In someembodiments of the methods provided herein the costimulatory agent is aCD-28, OX-40, 4-1BB, or CD40 antibody. In some embodiments of themethods provided herein, the method further includes administering oneor more vaccines. In some embodiments of the methods provided herein,the vaccine is a dendritic cell vaccine. In some embodiments of themethods provided herein, the method further includes administeringadoptive cell transfer therapy. In some embodiments of the methodsprovided herein, the adoptive cell transfer therapy is the use ofengineered T-cell receptors or chimeric antigen receptors. In someembodiments of the methods provided herein, the subject has aninfectious disease. In some embodiments of the methods provided herein,the infectious disease is a bacterial infection, a viral infection, aparasitic infection, or a fungal infection. In some embodiments of themethods provided herein, the infectious disease is a viral infection. Insome embodiments of the methods provided herein, the viral infection isHIV. In some embodiments of the methods provided herein, the infectionis an infection by a hepatitis virus. In some embodiments of the methodsprovided herein, the subject has an autoimmune disease or an allergicdisease. In some embodiments of the methods provided herein, thecomposition further includes one or more anti-inflammatory agents. Insome embodiments of the methods provided herein, the anti-inflammatoryis an NSAID. In some embodiments of the methods provided herein, thecomposition may be administered as one or more dose.

In one aspect, the disclosure provides a method that includesdetermining if one or more bacterial species of any of the compositionsprovided herein are present in the intestine of a subject, wherein ifless than 100%, less than 90%, less than 80%, less than 70%, less than60%, less than 50%, less than 40%, less than 30%, less than 20%, lessthan 10%, or none of the bacterial species are present, the compositionis administered to the subject. In some embodiments of the methodsprovided herein, the subject is undergoing, or will be undergoing,cancer treatment. In one aspect, the disclosure provides a method fordetermining if a subject is expected to respond positively to cancertreatment, wherein the method includes determining if one or morebacterial species of any of the compositions provided herein are presentin the intestine of a subject, wherein if less than 100%, less than 90%,less than 80%, less than 70%, less than 60%, less than 50%, less than40%, less than 30%, less than 20%, less than 10%, or none of thebacterial species are present, the subject is not expected to respondpositively to cancer treatment. In some embodiments of the methodsprovided herein, the cancer treatment is cancer immunotherapy treatment.In one aspect, the disclosure provides a method for reducing the risk ofa viral infection in a subject, wherein the method includes determiningif one or more bacterial species of any of the compositions providedherein are present in the intestine of a subject, wherein if less than100%, less than 90%, less than 80%, less than 70%, less than 60%, lessthan 50%, less than 40%, less than 30%, less than 20%, less than 10%, ornone of the bacterial species are present, the composition isadministered to the subject, thereby reducing the risk of a viralinfection in the subject.

In some embodiments of the methods provided herein, determining thepresence of one or more of the bacterial species is done by sequencingfecal matter of the subject. In some embodiments of the methods providedherein, determining the presence of one or more of the bacterial speciesis done by sequencing the 16S rDNA sequences of fecal matter of thesubject. In one aspect, the disclosure provides compositions and methodsto induce activation of CD8+ IFNγ-producing T-cells in the intestinaltract. In one aspect, the disclosure provides a composition comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 95% homology to the sequencesof the following NCBI accession numbers: LN998073, KR822463, CP011531,NR_112945, NZ-ACWW00000000, AB331897, AB261128, NZ-CAEG00000000,AB470343, AB595134, HE974920, NR_112933, AB490801, NZ-ACWB00000000,AY608696, CR626927, AB247141, NR_112935, AB249652, NR_113076 andAF139525. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 2, at least 3, at least 4,at least 5, at least 6, at least 7, at least 8, at least 9, at least 10,at least 11, at least 12, at least 13, at least 14, at least 15, atleast 16, at least 17, at least 18, at least 19, at least 20, or atleast 21 bacterial strains. In some embodiments of the compositionsprovided herein, the one or more bacterial strains comprises 16S rDNAsequences with at least 96%, at least 97%, at least 98%, or at least 99%homology with sequences provided herein.

In one aspect, the disclosure provides a composition that induces oractivates CD8+ IFNγ-producing T-cells, the composition comprising (i)one or more purified bacterial strains collected from human stool whichpossesses resistance to ampicillin, or (ii) a culture supernatant of(i). In some embodiments of the compositions provided herein, thecomposition comprises (a) a purified bacterial mixture comprising one ormore bacterial strains of species selected from the group consisting of

Phascolarctobacterium faecium; LN998073,

Fusobacterium ulcerans; KR822463,

Bacteroides dorei; CP011531,

Bacteroides uniformis; NR_112945,

Subdoligranulum sp. 4_3_54A2FAA; NZ-ACWW00000000,

Paraprevotella xylaniphila; AB331897,

Parabacteroides johnsonii; AB261128,

Alistipes sp. JC136; NZ-CAEG00000000,

Parabacteroides gordonii; AB470343,

Eubacterium limosum; AB595134,

Parabacteroides distasonis; HE974920,

Bacteroides cellulosilyticus; NR_112933,

Bacteroides clarus; AB490801,

Anaerostipes sp. 3_2_56FAA; NZ-ACWB00000000,

Bacteroides salyersiae; AY608696,

Bacteroides fragilis; CR626927,

Bacteroides uniformis; AB247141,

Bacteroides eggerthii; NR_112935,

Clostridium sp. TM-40; AB249652,

Parabacteroides goldsteinii; NR_113076, and

Bacteroides sp. AR29; AF139525, or (b) one or more bacterial strainscomprising a 16S rRNA sequence having at least 97% homology to a 16SrRNA sequence of a species selected from the group consisting of

Phascolarctobacterium faecium; LN998073,

Fusobacterium ulcerans; KR822463,

Bacteroides dorei; CP011531,

Bacteroides uniformis; NR_112945,

Subdoligranulum sp. 4_3_54A2FAA; NZ-ACWW00000000,

Paraprevotella xylaniphila; AB331897,

Parabacteroides johnsonii; AB261128,

Alistipes sp. JC136; NZ-CAEG00000000,

Parabacteroides gordonii; AB470343,

Eubacterium limosum; AB595134,

Parabacteroides distasonis; HE974920,

Bacteroides cellulosilyticus; NR_112933,

Bacteroides clarus; AB490801,

Anaerostipes sp. 3_2_56FAA; NZ-ACWB00000000,

Bacteroides salyersiae; AY608696,

Bacteroides fragilis; CR626927,

Bacteroides uniformis; AB247141,

Bacteroides eggerthii; NR_112935,

Clostridium sp. TM-40; AB249652,

Parabacteroides goldsteinii; NR_113076, and

Bacteroides sp. AR29; AF139525

In some embodiments of the compositions provided herein, the compositioncomprises a purified bacterial mixture comprising (a) one or morebacterial strains of species selected from the group consisting of

Phascolarctobacterium faecium; LN998073,

Fusobacterium ulcerans; KR822463,

Bacteroides dorei; CP011531,

Bacteroides uniformis; NR_112945,

Subdoligranulum sp. 4_3_54A2FAA; NZ-ACWW00000000,

Paraprevotella xylaniphila; AB331897,

Parabacteroides johnsonii; AB261128,

Alistipes sp. JC136; NZ-CAEG00000000,

Parabacteroides gordonii; AB470343,

Eubacterium limosum; AB595134, and

Parabacteroides distasonis; HE974920; or (b) one or more bacterialstrains comprising a 16S rRNA sequence of a species belonging to thegroup consisting of Phascolarctobacterium faecium; LN998073,

Fusobacterium ulcerans; KR822463,

Bacteroides dorei; CP011531,

Bacteroides uniformis; NR_112945,

Subdoligranulum sp. 4_3_54A2FAA; NZ-ACWW00000000,

Paraprevotella xylaniphila; AB331897,

Parabacteroides johnsonii; AB261128,

Alistipes sp. JC136; NZ-CAEG00000000,

Parabacteroides gordonii; AB470343,

Eubacterium limosum; AB595134, and

Parabacteroides distasonis; HE974920.

In some embodiments of the compositions provided herein, the CD8+IFNγ-producing T-cells express CD103 or Granzyme B.

In some embodiments of the compositions provided herein, the compositionactivates the immune system. In one aspect, the disclosure provides amethod for activating the immune system, the method comprisingadministration of one or more of the compositions provided herein. Inone aspect, the disclosure provides a method for activating CD8+IFNγ-producing T-cells, the method comprising administration of one ormore of the compositions provided herein to a subject. In one aspect,the disclosure provides a method for inducing the proliferation and/oraccumulation of CD8+ T cells in the intestine, comprising administeringto a subject any one or more of the compositions provided herein,wherein the administering results in the induction of proliferationand/or accumulation of CD8+ T cells in the intestine of the subject. Inone aspect, the disclosure provides a method for assisting in treatment,and/or preventing cancer or viral infection, comprising administering toa subject any one or more of the compositions provided herein, whereinthe administering prevents, treats, assists in treatment, and/orprevents cancer or viral infection. In one aspect, the disclosureprovides vaccine compositions which induce immune response againstbacterial strains of any one of the compositions disclosed herein. Inone aspect, the disclosure provides a vaccine composition containingantigen derived from constituents and/or metabolites of bacterialspecies of any one of the compositions provided herein.

In one aspect, the disclosure provides a method for inducing an immuneresponse in a subject, comprising administering to the subject any ofthe vaccines provided herein, wherein the administering results in theinduction of immune response of the subject. In one aspect, thedisclosure provides immune suppressive compositions. In one aspect, thedisclosure provides a composition comprising a chemical substance thatpossesses antibacterial activity towards bacterial species of any one ofthe compositions provided herein, or a chemical substance which binds aphysiologically active substance secreted from bacterial species of anyone of the compositions provided herein. In some embodiments of thecompositions provided herein, administration of the composition to asubject results in suppression of activity of CD8+ and IFNγ-producingT-cells in the subject. In one aspect, the disclosure provides a methodfor suppressing CD8+ and IFNγ-producing T-cells in the subject, themethod comprising administration of one or more of the compositionsprovided herein to the subject. In one aspect, the disclosure provides amethod for prevention, treatment or improvement in a disease originatedby over-activation of CD8+ and IFNγ-producing T-cells of the subject themethod comprising administering to the subject any one or more of thecompositions provided herein to the subject. In one aspect, thedisclosure provides substances derived from the bacterial strainsdisclosed herein. In one aspect, the disclosure provides aphysiologically active substance derived from a bacterial species of anyone of the compositions provided herein. In one aspect, the disclosureprovides a bacterial specific antigen of any one of the bacterialspecies of any one of the compositions provided herein.

In one aspect, the disclosure provides an antibody that specificallybinds a bacterial species of any one of the compositions providedherein. In one aspect, the disclosure provides a bacterial-specificnucleotide sequence contained in any one of the bacterial species of thecompositions provided herein. In one aspect, the disclosure providesanimal models and test kits. In one aspect, the disclosure provides ananimal model comprising a non-human mammal, wherein the intestinal tractof the non-human mammal has been inoculated with the bacterial speciesof any one of the compositions provided herein. In some embodiments ofthe animal model provided herein, the non-human mammal has a diseaseoriginated by irregularity of CD8+ IFNγ-producing T-cells. In oneaspect, the disclosure provides a kit for evaluating the activation ofCD8+ IFNγ-producing T cells, the kit comprising: intestinal epithelialcells, peripheral blood mononuclear cells, and a bacterial species ofany one of the compositions provided herein. In one aspect, thedisclosure provides methods of detection of CD8+ IFNγ-producing T cellsin the human intestinal tract. In one aspect, the disclosure provideskits for evaluating activation of CD8+ IFNγ-producing T cells. In someembodiments, the kits comprise intestinal epithelial cells, peripheralmononuclear cells, and the bacterial species of any of the compositionsdescribed herein.

In one aspect, the disclosure provides a method for screening bacteriaor a physiologically active substance derived from human intestinalbacteria, wherein the substance induces activation of CD8+IFNγ-producing T cells in the intestinal tract, comprising (i) allowinga non-human germ-free animal to ingest a physiologically activesubstance derived from human intestinal bacteria or bacteria, (ii)detecting the number, or activity of, CD8+ IFNγ-producing T cells in theintestinal tract of the non-human aseptic animal, wherein if activationof CD8+ IFNγ-producing T cells is detected, the physiologically activesubstance is identified as a substance that can activate CD8+IFNγ-producing T cells. In one aspect, the disclosure provides a methodfor screening bacteria or a physiologically active substance derivedfrom human intestinal bacteria a, wherein the substance inducesproliferation or activation of CD8+ IFNγ-producing T cells in intestinaltract, comprising (i) adding a physiologically active substance derivedfrom human intestinal bacteria or bacteria to the intestinal epithelialcells in a system comprising intestinal epithelial cells and peripheralblood mononuclear cells; (ii) detecting the number or activity of CD8+IFNγ-producing T cells in said system, wherein if the activation of CD8+IFNγ-producing T cells is detected, the physiologically active substanceis identified as a substance that can activate CD8+ IFN γ-producing Tcells.

In one aspect, the disclosure provides a method for screening for asubstance that induces activation of CD8+ IFNγ-producing T cells inintestinal tract, comprising (i) adding a physiologically activesubstance derived from bacteria or bacteria contained in a compositionprovided herein to a system containing intestinal epithelial cells andperipheral blood mononuclear cells, (ii) adding a test substance, (iii)detecting the number or activity of CD8+ IFNγ-producing T cells in saidsystem, wherein if the number or activity of CD8+ IFNγ-producing T cellsdetected in the is increased, the test substance is identified as asubstance that induces activation of CD8+ IFNγ-producing T cells. In oneaspect, the disclosure provides a method for screening a substance thatinduces activation of CD8+ IFNγ-producing T cells in intestinal tract,comprising (i) the method for screening a non-human animal providedherein, (ii) detecting the number or activity of CD8+ IFNγ-producing Tcells in the intestinal tract of the non-human animal, wherein if thenumber or activity of CD8+ IFNγ-producing T cells detected in the abovestep is increased, the test substance is identified as a substance thatinduces activation of CD8+ IFNγ-producing T cells. In one aspect, thedisclosure provides a composition for stimulating immunity, thecomposition comprising, as an active ingredient, a human intestinalbacterium or a physiologically active substance derived from a bacteriumobtained by the screening methods provided herein. In some embodimentsof the compositions provided herein, the composition induces theactivation of CD8+ IFNγ-producing T cells.

In one aspect, the disclosure provides a vaccine composition comprising,as an active ingredient, human intestinal bacteria obtained by any ofthe screening methods provided herein, or an antigen specific to saidbacterium. In one aspect, the disclosure provides a method for screeninga substance having an activity of inducing or exacerbating a diseasecaused by CD8+ IFNγ-producing T cells, comprising (i) allowing a testsubstance to be ingested by a non-human animal provided herein, (ii)detecting the degree of a disease-associated damage caused by CD8+IFNγ-producing T cells in said non-human animal, wherein the testsubstance is identified as a substance that induces a disease caused byCD8+ IFNγ-producing T cells when the extent of the lesion detected inthe above step is increased as compared to when no compound or placebowas added. In one aspect, the disclosure provides a composition forinducing or exacerbating a disease caused by CD8+ IFNγ-producing Tcells, wherein the composition comprises, as an active ingredient, thesubstance obtained by any one of the screening methods provided herein.In one aspect, the disclosure provides a composition comprising aprocessed human fecal sample, wherein the processed human fecal sampleis obtained by contacting a human fecal sample with ampicillin, andwherein the processed human fecal sample induces the proliferationand/or accumulation of CD8+ T-cells. In some embodiments, the disclosureprovides a method of treatment of a disease in a subject, the methodcomprising administering to the subject any one of the compositionsprovided herein in an effective amount to treat the disease in thesubject. In some embodiments of the methods provided herein, the diseaseis cancer or an infection (e.g., a viral infection).

In one aspect, the disclosure provides a method comprising inoculating ahuman fecal sample in germ free mice, and determining if the human fecalsample induces the proliferation and/or accumulation of CD8+ T-cells. Inone aspect, the disclosure provides a method for determining if a humanfecal sample induces proliferation and/or accumulation of CD8+ T cells,comprising inoculating germ-free mice with a human fecal sample, anddetermining if the human fecal sample induces the proliferation and/oraccumulation of CD8+ T-cells. In one aspect, the disclosure provides amethod for identifying a human fecal donor, comprising inoculatinggerm-free mice with a human fecal sample, and determining if the humanfecal sample induces the proliferation and/or accumulation of CD8+T-cells, wherein if the fecal sample induces the proliferation and/oraccumulation of CD8+ T-cells, the human subject is identified as a humanfecal donor. In one aspect, the disclosure provides a method foranalyzing expression levels of a marker in lymphocytes in a subject,comprising analyzing the expression levels of the marker, wherein themarker is induced by administering to the subject any of thecompositions described herein, wherein the marker is CD44, gp70 MC38peptide (KSPWFTTL; (SEQ ID NO: 53))-specific TCRβ, tumor antigen derivedligand-specific TCRβ, CD8, IFNγ, and/or GzmB.

In one aspect, the disclosure provides kits for analysis of expressionlevels of a marker in lymphocytes in a subject after induction, whereinthe marker is induced by administering to the subject any of thecompositions described herein, wherein the marker is CD44, gp70 MC38peptide (KSPWFTTL; (SEQ ID NO: 53))-specific TCRβ, tumor antigen derivedligand-specific TCRβ, CD8, IFNγ, and/or GzmB. In one aspect, thedisclosure provides methods for screening a bacteria or aphysiologically active substance derived from human intestinal bacteria,the method comprising, allowing a tumor-bearing non-human animal toingest a physiologically active substance derived from human intestinalbacteria or bacteria, detecting the expression of a marker, inlymphocytes isolated from the tumor-bearing non-human animal, wherein ifan increase in expression levels of the marker is detected, thephysiologically active substance is identified as an immunostimulatingagent for the tumor; and wherein the marker is CD44, gp70 MC38 peptide(KSPWFTTL; (SEQ ID NO: 53))-specific TCRβ, tumor antigen derivedligand-specific TCRβ, CD8, IFN and/or GzmB.

In one aspect, the disclosure provides a companion diagnostic method fortumor therapy with an immune checkpoint inhibitor, the method comprisinganalyzing expression levels of a marker in lymphocytes before and afterinduction by administering to the subject any of the compositionsdescribed herein with or without co-administration of the immunecheckpoint inhibitor, wherein if the expression levels of the marker inthe lymphocytes of the subject are increased by at least 10%, at least20%, at least 30%, at least 40%, at least 50%, at least 100%, or atleast 200% as compared to the expression levels in the lymphocytes ofthe subject before the administration of the composition,co-administration of the inhibitor and any of the compositions describedherein to the subject, the therapy is continued, wherein if theexpression levels in the lymphocytes of the subject are not increased ascompared to the expression levels in the lymphocytes of the subject,co-administration of the inhibitor and any of the compositions describedherein is discontinued or reanalyzed after repeating the administrationof any of the compositions described herein to the subject. In someembodiments, the methods further comprise analyzing expression levels oftumor antigen derived ligand-specific TCRβs in lymphocytes with specificantibodies that bind to the tumor antigen derived ligand-specific TCRβsor MHC multimers that bind to the tumor antigen derived ligand-specificTCRβs. In some embodiments, the methods are use in a tumor therapy withan immune checkpoint inhibitor, wherein the immune checkpoint inhibitoris a PD-1 inhibitor, PD-L1 inhibitor, or CTLA-4 inhibitor. In someembodiments, the methods further comprise assessing PD-1 expression inT-cells in the subject. In some embodiments, the methods furthercomprise assessing PD-L1 expression in cancer cells in the subject. Insome embodiments, the methods further comprise assessing CTLA-4expression in T-cells in the subject.

In one aspect, the disclosure provides kits for carrying out companiondiagnostic methods, wherein the kit comprises one or more molecules formonitoring of the expression levels of a marker in lymphocytes, whereinthe marker is CD44, gp70 MC38 peptide (KSPWFTTL; (SEQ ID NO:53))-specific TCRβ, tumor antigen derived ligand-specific TCRβ, CD8,IFNγ, and/or GzmB. In one aspect, the disclosure provides methods forevaluating the immune activation with the degree of IFNγ production insplenocytes, the method comprising administering to a subject any of thecompositions described herein. In one aspect, the disclosure provideskits for evaluating the immune activation with the degree of IFNγproduction in splenocytes, comprising one or more IFNγ marker moleculesand one or more bacterial species of any of the compositions describedherein. In one aspect, the disclosure provides methods for identifyingan immunostimulating agent for a tumor the method comprising screening ahuman intestinal bacteria or a physiologically active substance derivedfrom human intestinal bacteria, the method comprising, (i) allowing atumor-bearing non-human animal to ingest the human intestinal bacteriaor the physiologically active substance derived from the humanintestinal bacteria, and (ii) detecting IFNγ in splenocytes isolatedfrom the tumor-bearing non-human animal, wherein if induction of IFNγ isdetected, the human intestinal bacteria or physiologically activesubstance is identified as an immunostimulating agent for the tumor.

In one aspect, the disclosure provides a companion diagnostic method fortumor therapy with an immune checkpoint inhibitor, the method comprisingevaluating the immune activation with the degree of IFNγ production insplenocytes before and after induction by administering to the subjectany of the compositions described herein with or withoutco-administration of the inhibitor, wherein if the degree of IFNγproduction in the splenocytes in the subject is increased by at least10%, at least 20%, at least 30%, at least 40%, at least 50%, at least100%, or at least 200% as compared to the degree of IFNγ production inthe splenocytes in the subject before the administration of thecomposition, co-administration of the inhibitor and any of thecompositions described herein to the subject is continued, wherein ifthe degree of IFNγ production in the splenocytes of the subject is notincreased, the co-administration of the inhibitor and any of thecompositions described herein is discontinued or reanalyzed after repeatadministration of any of the compositions described herein to thesubject. In some embodiments, the method further comprises analyzingexpression levels of tumor antigens of the therapy target in splenocyteswith the specific antibodies or the MHC multimers. In some embodiments,the method is for tumor therapy with an immune checkpoint inhibitor,wherein the tumor inhibitor is a PD-1 inhibitor, PD-L1 inhibitor, orCTLA-4 inhibitor. In some embodiments, the method further comprisesassessing PD-1 expression in T-cells in the subject. In someembodiments, the method further comprises assessing PD-L1 expression incancer cells in the subject. In some embodiments, the method furthercomprises assessing CTLA-4 expression in T-cells in the subject.

In one aspect, the disclosure provides kits for carrying out thecompanion diagnostic methods described herein, comprising one or moreIFNγ marker molecules. In one aspect, the disclosure providescompositions comprising a purified bacterial mixture comprising one ormore bacterial strains of species selected from the group consisting ofPhascolarctobacterium faecium, Fusobacterium sp., Bacteroides dorei,bacterium IARFR67, Ruminococcaceae bacterium, Paraprevotellaxylaniphila, Parabacteroides johnsonii, Bacteroides sp., Parabacteroidesgordonii, Eubacterium limosum, Parabacteroides distasonis, Bacteroidescellulosilyticus, Bacteroides clarus, Anaerostipes caccae, Bacteroidessalyersiae, Bacteroides fragilis, Bacteroides uniformis, Bacteroideseggerthii, Clostridium sp., Parabacteroides goldsteinii, Bacteroidessp., Lachnospiraceae bacterium HGA0140, Hungatella hathewayi,Clostridium lavalense, Ruminococcus sp., and Clostridium innocuum. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 2, at least 3, at least 4, at least5, at least 6, at least 7, at least 8, at least 9, at least 10, at least11, at least 12, at least 13, at least 14, at least 15, at least 16, atleast 17, at least 18, at least 19, at least 20, at least 21, at least22, at least 23, at least 24, at least 25, or at least 26 bacterialstrains. In one aspect, the disclosure provides compositions comprisinga purified bacterial mixture comprising one or more bacterial strains ofspecies selected from the group consisting of Phascolarctobacteriumfaecium, Fusobacterium sp., Bacteroides dorei, bacterium IARFR67,Ruminococcaceae bacterium, Paraprevotella xylaniphila, Parabacteroidesjohnsonii, Bacteroides sp., Parabacteroides gordonii, Eubacterumlimosum, Parabacteroides distasonis, Bacteroides cellulosilyticus,Bacteroides clarus, Anaerostipes caccae, Bacteroides salyersiae,Bacteroides fragilis, Bacteroides uniformis, Bacteroides eggerthii,Clostridium sp., Parabacteroides goldsteinii, and Bacteroides sp. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 2, at least 3, at least 4, at least5, at least 6, at least 7, at least 8, at least 9, at least 10, at least11, at least 12, at least 13, at least 14, at least 15, at least 16, atleast 17, at least 18, at least 19, at least 20, or at least 21bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strains ofspecies selected from the group consisting of Phascolarctobacteriumfaecium, Fusobacterium sp., Bacteroides dorei, bacterium IARFR67,Ruminococcaceae bacterium, Paraprevotella xylaniphila, Parabacteroidesjohnsonii, Bacteroides sp., Parabacteroides gordonii, Eubacterumlimosum, and Parabacteroides distasonis. In some embodiments of thecompositions provided herein, the purified bacterial mixture comprisesat least 2, at least 3, at least 4, at least 5, at least 6, at least 7,at least 8, at least 9, at least 10, or at least 11 bacterial strains.In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strains ofspecies selected from the group consisting of Phascolarctobacteriumfaecium, Fusobacterium sp., Ruminococcaceae bacterium, and Eubacterumlimosum. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 2, at least 3, or at least4 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strains ofspecies selected from the group consisting of Bacteroides dorei,bacterium IARFR67, Paraprevotella xylaniphila, Parabacteroidesjohnsonii, Bacteroides sp., Parabacteroides gordonii, andParabacteroides distasonis. In some embodiments of the compositionsprovided herein, the purified bacterial mixture comprises at least 2, atleast 3, at least 4, at least 5, at least 6, or at least 7 bacterialstrains.

Each of the limitations of the invention can encompass variousembodiments of the invention. It is, therefore, anticipated that each ofthe limitations of the invention involving any one element orcombinations of elements can be included in each aspect of theinvention. This invention is not limited in its application to thedetails of construction and the arrangement of components set forth inthe following description or illustrated in the drawings. The inventionis capable of other embodiments and of being practiced or of beingcarried out in various ways.

BRIEF DESCRIPTION OF DRAWINGS

The accompanying drawings are not intended to be drawn to scale. Thefigures are illustrative only and are not required for enablement of thedisclosure. For purposes of clarity, not every component may be labeledin every drawing. In the drawings:

FIGS. 1A and 1B show data of experiments with lymphocytes that wereisolated from small intestine (SI) and colon mucosal lamina propria ofSPF and germ-free (GF) mice and stimulated with PMA/ionomycin for 3.5hours. CD3, TCRβ, CD8 and IFNγ were stained with antibodies and analyzedby flow cytometry. (FIG. 1A) The expression of CD8 and IFNγ by the gatedCD3 and TCRβ positive cells of representative mice. (FIG. 1B) Summarizeddata of the percentages of IFNγ positive cells within CD3, TCRβ and CD8+cells. Each plot represents individual mice. ** P<0.01 (Student'st-test).

FIGS. 2A and 2B show data of experiments with lymphocytes that wereisolated from the small intestinal mucosal lamina propria of SPF andgerm-free mice and stimulated with PMA/ionomycin for 3.5 hours. CD3,TCRβ, CD8, CD103, IFNγ and GzmB were stained with antibodies andanalyzed by flow cytometry. (FIG. 2A) The expression of IFNγ and CD103(upper row) or GzmB (lower row) by the gated CD8 T cells ofrepresentative mice. (FIG. 2B) Summarized data of the percentages ofeach IFNγ positive cell fraction in CD3, TCRβ and CD8+ cells. Each plotrepresents individual mice. * P<0.05 (Student's t-test).

FIGS. 3A and 3B show data of experiments with lymphocytes that wereisolated from small intestine (SI) and large intestine (Colon) mucosallamina propria of SPF mice delivered from different laboratory animalfacilities and stimulated with PMA/ionomycin for 3.5 hours. CD3, TCRβ,CD8 and IFNγ were stained with antibodies and analyzed by flowcytometry. (FIG. 3A) The expression of CD8 and IFNγ by the gated CD3 andTCRβ positive cells of representative mice. (FIG. 3B) Summarized data ofthe percentages of IFNγ positive cells in CD3, TCRβ and CD8+ cells. Eachplot represents individual mice. * P<0.05, ** P<0.01 (one-way ANOVA).

FIGS. 4A and 4B show data of experiments in which after co-housing ofSPF mice from Charles River Laboratories with CLEA Japan for 2 or 6weeks, lymphocytes were isolated from intestinal (SI) and colon mucosallamina propria and stimulated with PMA/ionomycin for 3.5 h. CD3, TCRβ,CD8 and IFNγ were stained with antibodies and analyzed by flowcytometry. (FIG. 4A) The expression of CD8 and IFNγ by the gated CD3 andTCRβ positive cells of representative mice. (FIG. 4B) Summarized data ofthe percentages of IFNγ positive cells in CD3, TCRβ and CD8+ cells. Eachplot represents individual mice. * P<0.05, ** P<0.01 (one-way ANOVA).

FIGS. 5A and 5B show data of experiments with stools from healthyvolunteers (A˜F) which were orally administered into germ free miceindividually in sterile vinyl isolators. Four weeks later, lymphocyteswere isolated from the lamina propria of the large intestine andstimulated with PMA/ionomycin for 3.5 hours. CD3, TCRβ, CD8 and IFNγwere stained with antibodies and analyzed by flow cytometry. (FIG. 5A)The expression of CD8 and IFNγ by the gated CD3 and TCRβ positive cellsof representative mice. (FIG. 5B) Summarized data of the percentages ofIFNγ positive cells in CD3, TCRβ and CD8+ cells. Each plot representsindividual mice. ** P<0.01 (one-way ANOVA).

FIGS. 6A and 6B show data of experiments with the cecal contents of B #5mouse, which was orally administered to germ free mice. One day later,their drinking waters were switched to ampicillin (AMP), metronidazole(MNZ), streptomycin (STM) or tylosin (Tylo.) until the end ofexperiment. The contents of the cecum of B #5 treated with 3% ofchloroform were administered to germ free mice. Four weeks later,lymphocytes were isolated from the lamina propria of the large intestineand stimulated with PMA/ionomycin for 3.5 hours. CD3, TCRβ, CD8, IFNγwere stained with antibodies and analyzed by flow cytometry. (FIG. 6A)The expression of CD8 and IFNγ by the gated CD3 and TCRβ positive cellsof representative mice. (FIG. 6B) Summarized data of the percentages ofIFNγ positive cells in CD3, TCRβ and CD8+ cells. Each plot representsindividual mice. * P<0.05 (one-way ANOVA).

FIGS. 7A and 7B show 16S rRNA gene sequence data of the cecal microbiotaof the mice prepared in FIGS. 6A and 6B, which were comprehensivelyanalyzed using the next generation sequencer. (FIG. 7A) Figure of theproportion of operational taxonomic unit (OTU). On the right end, theOTU corresponding to the isolated strains of the B #5-AMP-2 mouse isshown in green. (FIG. 7B) Identification of isolated strains and thehomologous bacterial name (Closest sequence) and similarity (S-ab score)are shown.

FIGS. 8A and 8B show data on the mixture of 21 isolated strains whichwas orally administered to germ free mice. Four weeks later, lymphocyteswere isolated from the lamina propria of the large intestine andstimulated with PMA/ionomycin for 3.5 hours. CD3, TCRβ, CD8 and IFNγwere stained with antibodies and analyzed by flow cytometry. (FIG. 8A)The expression of CD8 and IFNγ by the gated CD3 and TCRβ positive cellsof representative mice. (FIG. 8B) Summarized data of the percentages ofIFNγ positive cells in CD3, TCRβ and CD8+ cells. Each plot representsindividual mice. ** P<0.01 (Student's t-test).

FIGS. 9A and 9B show data on the mixture of 21 isolated strains whichwas orally administered to germ free mice. Four weeks later, lymphocyteswere isolated from the lamina propria of the large intestine andstimulated with PMA/ionomycin for 3.5 hours. CD3, TCRβ, CD8, CD103, IFNγand GzmB were stained with antibodies and analyzed by flow cytometry.(FIG. 9A) The expression of IFNγ and CD103 (upper row) or GzmB (lowerrow) by the gated CD8 T cells of representative mice. (FIG. 9B)Summarized data of the percentages of each IFNγ positive cell fractionin CD3, TCRβ and CD8+ cells. Each plot represents individual mice. *P<0.05, ** P<0.01 (Student's t-test).

FIGS. 10A and 10B show data on the mixture of the 21 strains or 11strains (11 strain mixture corresponds to strains #1-11; See Table 1),which were orally administered to germ free mice. Four weeks later,lymphocytes were isolated from the lamina propria of the large intestineand stimulated with PMA/ionomycin for 3.5 hours. CD3, TCRβ, CD8 and IFNγwere stained with antibodies and analyzed by flow cytometry. (FIG. 10A)The expression of CD8 and IFNγ by the gated CD3 and TCRβ positive cellsof representative mice. (FIG. 10B) Summarized data of the percentages ofIFNγ positive cells in CD3, TCRβ and CD8+ cells. Each plot representsindividual mice. *** P<0.001, ****P<0.0001 (one-way ANOVA).

FIG. 11 shows the compositions of the 10-mix and 11-mix bacterialstrains that were inoculated into GF mice (See FIGS. 12A and 12B).

FIGS. 12A and 12B show data obtained from mixtures of 11 or 10 strains(see FIG. 11), or a mixture of 17 strains that are known Treg-inducers,which were orally administered to germ free mice. Four weeks later,lymphocytes were isolated from the lamina propria of the large intestineand stimulated with PMA/ionomycin for 3.5 hours. CD3, TCRβ, CD8 and IFNγwere stained with antibodies and analyzed by flow cytometry. (FIG. 12A)The expression of CD8 and IFNγ by the gated CD3 and TCRβ positive cellsof representative mice. (FIG. 12B) Summarized data of the percentages ofCD8+ IFN+ cells in CD3+ TCRβ+ cells (left), IFNγ+ cells in CD8T cells(middle) and the numbers of CD8+ IFNγ+ cells (right). Each plotrepresents individual mice. ** P<0.01, *** P<0.001, ****P<0.0001(one-way ANOVA).

FIG. 13 shows a phylogenetic tree which was constructed from the 16SrRNA gene sequences of the 11 strains (See FIG. 11), their closestsequences and some type strains using the MEGA v5.0 package and theneighbor-joining method. The strains which were inoculated into GF miceas a 7 mix or 4 mix are shown as well (The results of the inoculationexperiments are shown in FIGS. 14A and 14B).

FIGS. 14A and 14B show data of the mixtures of the 11 strains, 7 or 4strains mixtures listed in FIG. 13, which were orally administered togerm free mice. Four weeks later, lymphocytes were isolated from thelamina propria of the large intestine and stimulated with PMA/ionomycinfor 3.5 hours. CD3, TCRβ, CD8 and IFNγ were stained with antibodies andanalyzed by flow cytometry. (FIG. 14A) The expression of CD8 and IFNγ bythe gated CD3 and TCRβ positive cells of representative mice. (FIG. 14B)Summarized data of the percentages of CD8+ IFNγ+ cells in CD3+ TCRβ+cells (left), IFNγ+ cells in CD8T cells (middle) and the numbers of CD8+IFNγ+ cells (right). Each plot represents individual mice. * P<0.05, **P<0.01, *** P<0.001 (one-way ANOVA).

FIG. 15 shows data on experiments with six weeks-old SPF C57BL/6 mice,which were purchased from Japan SLC and treated with antibiotics (1 g/LAmpicillin, 0.5 g/L Vancomycin, 1 g/L Metronidazole and 1 g/L Neomycin;“AVMN”) in their drinking water. Then, mice were subcutaneously injectedinto the right flank with 3×105 MC38 tumor cells line at day 0. Whentumors appeared and were palpable, antibiotics treatment was stopped(day 2). Mice were injected intraperitoneally with 200 μg of anti-PD1antibody (clone J43) at day 3, 5 and 9 (“+anti-PD1Ab”). Mice weregavaged with the 11 mix 2 or 3 times a week including day 3, 5 and 9(“+11 mix”). Tumor size was measured using a caliper and tumor volumewas determined as length×width2×0.5. ** P<0.01, *** P<0.001, ****P<0.0001 (two-way ANOVA).

FIGS. 16A and 16B show data on lymphocytes isolated from tumor cells. Atday 23 or 27, lymphocytes were isolated from tumors and stimulated withPMA/ionomycin for 4 hours. CD3, TCRβ, CD8 and IFNγ were stained withantibodies and analyzed by flow cytometry. (FIG. 16A) The expression ofCD8 and IFNγ by the gated CD3 and TCRβ positive cells of representativemice. (FIG. 16B) Summarized data of the percentages of CD8+ IFNγ+ cellsin CD3+ TCRβ+ cells (left), IFNγ+ cells in CD8T cells (middle) and thenumbers of CD8+ IFNγ+ cells (right). Each plot represents individualmice. * P<0.05, ** P<0.01, *** P<0.001 (one-way ANOVA).

FIGS. 17A, 17B show data on lymphocytes isolated from tumor cells. Atday 23 or 27, lymphocytes were isolated from tumors and stimulated withPMA/ionomycin for 4 hours. CD3, TCRβ, CD8, gp70 MC38 peptide (KSPWFTTL(SEQ ID NO: 53))-specific TCRβ, CD44, GzmB and IFNγ were stained withantibodies and peptide-H2Kb tetramer, and analyzed by flow cytometry.(FIG. 17A) The expression of gp70-specific TCRβ, CD44, GzmB and IFNγ bythe gated CD3, TCRβ and CD8+ cells of representative mice. (FIG. 17B).Summarized data of the percentages of each IFN positive cell fraction inCD8T cells. Each plot represents individual mice. ** P<0.01, ***P<0.001, **** P<0.0001 (one-way ANOVA).

FIG. 18 shows data on lymphocytes isolated from tumor cells. The effecton IFNγ+CD4 T cells is shown in FIG. 18.

FIG. 19 shows data on lymphocytes isolated from tumor cells. At day 23or 27, whole splenocytes were isolated and plated at 106 cells per welland stimulated with 0.5 μg/mL gp70 MC38 peptide (KSPWFTTL (SEQ ID NO:53)) for 36 hours at 37° C. Spots were developed using the Mouse IFNγELISPOT Ready-SET Go!R kit (eBioscience), and the number of spots wasmeasured using an Immunospot Series 4 Analyzer and analyzed usingImmunoSpot software (Cellular Technology). Each plot representsindividual mice. “Naive” is a mouse which was not treated withantibiotics, not injected with MC38 cells and not treated with 11mix andanti-PD1 antibody. * P<0.05, ** P<0.01, *** P<0.001 (one-way ANOVA).

FIG. 20 shows data on 26 isolated strains, including 11 selectedstrains.

FIG. 21 shows data on induction of GzmB+ IFNγ+CD8 T cells by 11-mixbacterial strains.

FIG. 22 shows that slower tumor growth was accompanied by increasedinfiltration of IFNγ+CD8 T cells into the tumor.

FIG. 23 shows that the combination of αPD1 Ab and 11-mix bacterialstrains boosted infiltration of GzmB+ IFNγ+CD8 cytotoxic T cells intothe tumor.

FIG. 24 shows a schematic of the experimental plan described in Example4 relating to treatment with the 11-mix and/or an anti-CTLA-4 antibody.

FIG. 25 shows body weight of mice that received the combination of αCTLA-4 Ab and the 11-mix of bacterial strains (left panel). Mice thatreceived the combination of α CTLA-4 Ab and the 11-mix of bacterialstrains had a significant reduction in tumor growth (right panel) in theexperiment presented in FIG. 24 (Example 4).

FIG. 26 shows that the combination of αCTLA-4 Ab and the 11-mix ofbacterial strains had a significant effect on the survival of the micein the experiment presented in FIG. 24 (Example 4).

FIG. 27 shows tumor volume plots of individual mice treated in theexperiments described in Example 4 (control, 11-mix; αCTLA-4 Ab;11-mix+αCTLA-4 Ab).

FIG. 28 shows a schematic of the experimental plan described in Example5 relating to treatment with the 11-mix or 4-mix and/or an anti-PD-1antibody.

FIG. 29 shows body weight (left panel) and tumor volume (right panel) ofmice that received the combination of α PD1 Ab and the 4-mix ofbacterial strains or α PD1 Ab and the 11-mix of bacterial strains, andthe various control groups.

FIG. 30 shows tumor volume plots of individual mice treated inexperiments of Example 5 (11-mix; α PD-1 Ab; 11-mix+α PD-1 Ab). Thetumor volume did not increase in multiple animals in the 11-mix+αPD-1 Abtreatment group (bottom right panel).

FIG. 31 shows survival plots of mice treated in experiments of Example 5(11-mix; αPD-1 Ab; 11-mix+αPD-1 Ab).

FIG. 32 shows tumor volume plots of individual mice treated inexperiments of Example 5 (4-mix; αPD-1 Ab; 4-mix+αPD-1 Ab). The tumorvolume did not increase in multiple animals in the 4-mix+αPD-1 Abtreatment (bottom right panel).

FIG. 33 shows plots of mice treated in experiments of Example 5.Highlighted are treatment with αPD-1 Ab, 11-mix+αPD-1 Ab, and4-mix+αPD-1 Ab.

FIG. 34 shows data of experiments with the Braf Pten melanoma model(Example 6). Briefly, mice were administered antibiotics (“AVMN”) fromday −3 to day 2 and engrafted with 7×105 Braf Pten cells on day 0. Ondays 3, 6, and 9 the indicated groups of mice were administered ananti-PD1 antibody (arrows on the timeline) and SLC SPF feces fromspecific-pathogen free (SPF) mice obtained from Japan SLC (SLC SPFfeces), with or without the 11-mix (arrows with asterisk on thetimeline). The groups of mice indicated as having received the 11-mixwere administered the 11-mix 2 or 3 times per week. The plot shows theaverage tumor volume at each of the timepoints for the groups ofmice**** P<0.0001, *** P<0.001 (two-way ANOVA).

FIG. 35 shows data of experiments with the Braf Pten melanoma model(Example 6). Briefly, mice were administered antibiotics (“AVMN”) fromday −3 to day 2 and engrafted with 7×105 Braf Pten cells on day 0. Ondays 3, 6, and 9 the indicated groups of mice were administered ananti-PD1 antibody (arrows on the timeline) and SLC SPF feces fromspecific-pathogen free (SPF) mice obtained from Japan SLC (SLC SPFfeces), with or without the 11-mix (arrows with asterisk on thetimeline). The groups of mice indicated as having received the 11-mixwere administered the 11-mix 2 or 3 times per week. The plot shows theaverage tumor area at each of the timepoints for the groups of mice.**** P<0.0001, *** P<0.001 (two-way ANOVA).

FIG. 36 shows data on the weight of tumors obtained on days 22 and 24from the indicated groups of mice. * P<0.05 (one-way ANOVA).

FIGS. 37A-37C show data on lymphocytes isolated from tumor cells. Ondays 22 and 24, lymphocytes were isolated from tumors. CD3, TCRβ, CD8,and IFNγ were stained with antibodies. FIG. 37A shows the percentage ofCD8+ IFNγ+ cells in the CD3+ TCRβ+ CD8α+ population of cells isolatedfrom the tumors. FIG. 37B shows the number of CD8+ IFNγ+ cells isolatedfrom the tumors. FIG. 37C shows the number of CD8+ IFNγ+ cells per gramof tumors. ** P<0.01, * P<0.05 (one-way ANOVA).

FIG. 38 shows the percentage of IFNγ+ cells in the population of CD8Tcells isolated from the tumors. *** P<0.001, ** P<0.01, * P<0.05(one-way ANOVA).

FIGS. 39A-39D show data on lymphocytes isolated from tumor cells. Ondays 22 and 24, lymphocytes were isolated from tumors. CD3, TCRβ, CD8,IFNγ, GzmB, IL-17, and CD4 were stained with antibodies. FIG. 39A showsthe percentage of IFNγ+ GzmB+ cells in the CD3+ TCRβ+CD8α+ population ofcells isolated from the tumors. FIG. 39B shows the percentage of Th1cells in the CD3+ TCRβ+CD4+ population of cells isolated from thetumors. FIG. 39C shows the percentage of Th17 cells in the CD3+ TCRβ+CD4+ population of cells isolated from the tumors. FIG. 39D shows thepercentage of Treg cells in the CD3+ TCRβ+ CD4+ population of cellsisolated from the tumors.

FIG. 40 shows a schematic of the experimental plan described in Example7 (the dosing study).

FIGS. 41A-41C show data on lymphocytes isolated from mice in theexperiment shown in FIG. 40 (Example 7). CD3, TCRβ, CD8, and IFNγ werestained with antibodies. FIG. 41A shows the percentage of CD8+ IFNγ+cells in the CD3+ TCRβ+ CD8α+ population of cells isolated from theindicated mice. FIG. 41B shows the number of CD8+ IFNγ+ cells isolatedfrom the indicated mice. FIG. 41C shows the percentage of IFNγ+ cells inthe population of CD8T cells isolated from the indicated mice.

FIGS. 42A-42C show data on lymphocytes isolated from mice from theexperiment shown in FIG. 40 (Example 7). CD3, TCRβ, CD8, IFNγ, CD103,IL-17, and CD4 were stained with antibodies. FIG. 42A shows thepercentage of IFNγ+CD103+ cells in the CD3+ TCRβ+ CD8α+ population ofcells isolated from the indicated mice. FIG. 42B shows the percentage ofTh17 cells in the CD3+ TCRβ+CD4+ population of cells isolated from theindicated mice. FIG. 42C shows the percentage of Th1 cells in the CD3+TCRβ+ CD4+ population of cells isolated from the indicated mice.

FIGS. 43A-43C and 44 show the results from the experiments of Example 8.The experiments show that BATF3 is required for the 11-mix to induceCD8−T cells. BATF3 is not required to induce Th17. FIG. 43A shows thepercentage of IFNγ+ in the CD3+ TCRβ+CD8α+ (CD8 T cell) population ofcells isolated from the indicated mice. FIG. 43B shows the number ofCD8+ IFNγ+ cells. FIG. 43C shows the percentage of Th17 cells in theCD3+ TCRβ+CD4+ population of cells isolated from the indicated mice.**** P<0.0001, *** P<0.001, ** P<0.01, * P<0.05 (one-way ANOVA).

FIG. 44 shows that BATF3 is required for the 11-mix to induce CD8−Tcells, as evidenced by the flow cytometry (FIG. 44A), and the percentageof IFNγ+ in the CD3+ TCRβ+ CD8α+ (CD8 T cells) population of cellsisolated from the indicated mice (FIG. 44B).

FIGS. 45-46 show the results from the experiments of Example 9. Theexperiments show that the 11-mix is effective in treating Listeriainfections. FIG. 45 shows that feces+11-mix is effective in clearingListeria from infected mice, as evidenced in a decrease in the amount ofListeria CFUs in the feces.

FIG. 46 shows that the body weight of Listeria infected mice treatedwith feces and the 11-mix is higher than treatment with feces only.

FIGS. 47A and 47B shows data relating to Example 2. The mixtures of the11 strains, 7 or 4 strains mixtures listed in FIG. 13, were orallyadministered to germ free mice. Four weeks later, lymphocytes wereisolated from the lamina propria of the large intestine and stimulatedwith PMA/ionomycin for 3.5 hours. CD3, TCRβ, CD8 and IFNγ were stainedwith antibodies and analyzed by flow cytometry (FIG. 47A). Theexpression of CD8 and IFNγ by the gated CD3 and TCRβ positive cells ofrepresentative mice is show in FIG. 47B, as indicated by the percentageof IFNγ+ cells in CD8T cells. Each plot represents individual mice. *P<0.05, ** P<0.01, *** P<0.001 (one-way ANOVA).

FIG. 48 relates to Example 10 and shows that the CD8 induction effect ofthe 11-mix in mice that are not otherwise challenged is limited to theintestine/gut compartment. (SI=short intestine, CIEL=colonicintraepithelial lymphocytes, LN=lymph nodes)

FIG. 49 shows that the frequencies of DC subsets in colonic LP were onlyslightly changed by the colonization with 11-mix.

FIGS. 50-52 show that MHC CLP class cells are activated by theadministration of the 11-mix, and that the activation is strongestwithin the first week of activation. There is no activation of the MHCMLN class cells. The individual measurements are shown in FIGS. 50 and51, while the accumulated data are depicted in FIG. 52.

FIGS. 50-52 show that MHC CLP class cells are activated by theadministration of the 11-mix, and that the activation is strongestwithin the first week of activation. There is no activation of the MHCMLN class cells. The individual measurements are shown in FIGS. 50 and51, while the accumulated data are depicted in FIG. 52.

FIGS. 50-52 show that MHC CLP class cells are activated by theadministration of the 11-mix, and that the activation is strongestwithin the first week of activation. There is no activation of the MHCMLN class cells. The individual measurements are shown in FIGS. 50 and51, while the accumulated data are depicted in FIG. 52.

FIGS. 53 and 54 show that MHC CLP class cells are activated by theadministration of the 11-mix, while there is no activation of the MHCMLN class cells. The individual measurements are shown in FIG. 53, whilethe accumulated data are depicted in FIG. 54 expressed as percentage ofCD3+ TCDRbeta+CD8alpha+ cells.

FIGS. 53 and 54 show that MHC CLP class cells are activated by theadministration of the 11-mix, while there is no activation of the MHCMLN class cells. The individual measurements are shown in FIG. 53, whilethe accumulated data are depicted in FIG. 54 expressed as percentage ofCD3+ TCDRbeta+ CD8alpha+ cells.

FIG. 55 shows that MHC CLP class cells are activated by theadministration of the 11-mix, as evidenced by Ki67 status, while thereis no activation of the MHC MLN class cells.

FIGS. 56 and 57 show that MHC CLP class cells are activated by theadministration of the 11-mix, as evidenced by CD103+ status, while thereis no activation of the MHC MLN class cells. The individual measurementsare shown in FIG. 56, while the accumulated data are depicted in FIG. 57expressed as percentage of CD3+ TCRβeta+ CD8alpha+ IFNγ+ cells.

FIGS. 56 and 57 show that MHC CLP class cells are activated by theadministration of the 11-mix, as evidenced by CD103+ status, while thereis no activation of the MHC MLN class cells. The individual measurementsare shown in FIG. 56, while the accumulated data are depicted in FIG. 57expressed as percentage of CD3+ TCRβeta+ CD8alpha+ IFNγ+ cells.

DESCRIPTION OF EMBODIMENTS Detailed Description

Provided herein are compositions and methods for the induction and/orproliferation of CD8+ T-cells, and methods for the treatment of diseasesand conditions that can be treated through the induction and/orproliferation of CD8+ T-cells, including infectious diseases andcancers. In one aspect, the disclosure provides compositions comprisingone or more bacterial strains with unique biological properties. In oneaspect, the compositions of the bacterial strains disclosed herein, alsoreferred to as bacterial compositions, can induce the proliferationand/or accumulation of CD8+ T-cells. In one aspect, the compositions ofthe bacterial strains disclosed herein can induce the proliferationand/or accumulation of CD8+ T-cells.

In one aspect, the bacteria of the compositions disclosed herein can beidentified by their 16S rRNA (or 16S rDNA) nucleic acid sequence. Ingeneral, bacteria are classified as belonging to a specific speciesand/or genus based on their 16S rRNA nucleic acid sequence. Bacteria,such as bacteria derived from the microbiome, may also be classifiedinto phylogenetic clusters with other closely related strains andspecies. (See e.g., Rajilic-Stojanovic, M., and de Vos, W. M. (2014).The first 1000 cultured species of the human gastrointestinalmicrobiota. FEMS Microbiol Rev 38, 996-1047). Methods for determiningthe identity of specific bacterial species based on their 16S rRNA (or16S rDNA) nucleic acid sequence are well known in the art (See e.g.,Jumpstart Consortium Human Microbiome Project Data Generation Working,G. (2012). Evaluation of 16S rDNA-based community profiling for humanmicrobiome research. PLoS One 7, e39315). In one aspect, the disclosureprovides compositions comprising a purified bacterial mixture comprisingone or more bacterial strains comprising 16S rDNA sequences of at least97% homology to SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ IDNO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ IDNO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ IDNO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ IDNO:25, or SEQ ID NO:26. In some embodiments of the compositions providedherein, the purified bacterial mixture comprises at least 2, at least 3,at least 4, at least 5, at least 6, at least 7, at least 8, at least 9,at least 10, at least 11, at least 12, at least 13, at least 14, atleast 15, at least 16, at least 17, at least 18, at least 19, at least20, at least 21, at least 22, at least 23, at least 24, at least 25, orat least 26 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ IDNO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11,SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16,SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21,SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, or SEQ ID NO:26.In some embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 2, at least 3, at least 4, at least5, at least 6, at least 7, at least 8, at least 9, at least 10, at least11, at least 12, at least 13, at least 14, at least 15, at least 16, atleast 17, at least 18, at least 19, at least 20, at least 21, at least22, at least 23, at least 24, at least 25, or at least 26 bacterialstrains. In one aspect, the disclosure provides compositions comprisinga purified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% homology to SEQ ID NO:1,SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ IDNO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ IDNO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ IDNO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ IDNO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, or SEQ ID NO:26. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, at least 7, at least 8, at least 9, at least 10, at least 11, atleast 12, at least 13, at least 14, at least 15, at least 16, at least17, at least 18, at least 19, at least 20, at least 21, at least 22, atleast 23, at least 24, at least 25, or at least 26 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ IDNO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11,SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16,SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21,SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, or SEQ ID NO:26.In some embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, at least 7, at least 8, at least 9, at least 10, at least 11, atleast 12, at least 13, at least 14, at least 15, at least 16, at least17, at least 18, at least 19, at least 20, at least 21, at least 22, atleast 23, at least 24, at least 25, or at least 26 bacterial strains. Inone aspect, the disclosure provides compositions comprising a purifiedbacterial mixture comprising one or more bacterial strains comprising16S rDNA sequences of at least 97% homology to SEQ ID NO:1, SEQ ID NO:2,SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ IDNO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ IDNO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ IDNO:18, SEQ ID NO:19, SEQ ID NO:20, and SEQ ID NO:21. In some embodimentsof the compositions provided herein, the purified bacterial mixturecomprises at least 2, at least 3, at least 4, at least 5, at least 6, atleast 7, at least 8, at least 9, at least 10, at least 11, at least 12,at least 13, at least 14, at least 15, at least 16, at least 17, atleast 18, at least 19, at least 20, or at least 21 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ IDNO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11,SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16,SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, and SEQ IDNO:21. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 2, at least 3, at least 4,at least 5, at least 6, at least 7, at least 8, at least 9, at least 10,at least 11, at least 12, at least 13, at least 14, at least 15, atleast 16, at least 17, at least 18, at least 19, at least 20, or atleast 21 bacterial strains. In one aspect, the disclosure providescompositions comprising a purified bacterial mixture comprising two ormore bacterial strains comprising 16S rDNA sequences of at least 97%homology to SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ IDNO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10,SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15,SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20,and SEQ ID NO:21. In some embodiments of the compositions providedherein, the purified bacterial mixture comprises at least 3, at least 4,at least 5, at least 6, at least 7, at least 8, at least 9, at least 10,at least 11, at least 12, at least 13, at least 14, at least 15, atleast 16, at least 17, at least 18, at least 19, at least 20, or atleast 21 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ IDNO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11,SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16,SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, and SEQ IDNO:21. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 3, at least 4, at least 5,at least 6, at least 7, at least 8, at least 9, at least 10, at least11, at least 12, at least 13, at least 14, at least 15, at least 16, atleast 17, at least 18, at least 19, at least 20, or at least 21bacterial strains. In one aspect, the disclosure provides compositionscomprising a purified bacterial mixture comprising one or more bacterialstrains comprising 16S rDNA sequences of at least 97% homology to SEQ IDNO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6,SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, or SEQ ID NO:11. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 2, at least 3, at least 4, at least5, at least 6, at least 7, at least 8, at least 9, at least 10, or atleast 11 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ IDNO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, or SEQ IDNO:11. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 2, at least 3, at least 4,at least 5, at least 6, at least 7, at least 8, at least 9, at least 10,or at least 11 bacterial strains. In one aspect, the disclosure providescompositions comprising a purified bacterial mixture comprising one ormore bacterial strains comprising 16S rDNA sequences of at least 97%sequence identity with SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ IDNO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ IDNO:62, SEQ ID NO:63, or SEQ ID NO:64. In some embodiments of thecompositions provided herein, the purified bacterial mixture comprisesat least 2, at least 3, at least 4, at least 5, at least 6, at least 7,at least 8, at least 9, at least 10, or at least 11 bacterial strains.In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% homology to SEQ ID NO:1,SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ IDNO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, or SEQ ID NO:11. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 3, at least 4, at least 5, at least 6, atleast 7, at least 8, at least 9, at least 10, or at least 11 bacterialstrains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ IDNO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, or SEQ IDNO:11. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 3, at least 4, at least 5,at least 6, at least 7, at least 8, at least 9, at least 10, or at least11 bacterial strains. In one aspect, the disclosure providescompositions comprising a purified bacterial mixture comprising two ormore bacterial strains comprising 16S rDNA sequences of at least 97%sequence identity with SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ IDNO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ IDNO:62, SEQ ID NO:63, or SEQ ID NO:64. In some embodiments of thecompositions provided herein, the purified bacterial mixture comprisesat least 3, at least 4, at least 5, at least 6, at least 7, at least 8,at least 9, at least 10, or at least 11 bacterial strains. In oneaspect, the disclosure provides compositions comprising a purifiedbacterial mixture comprising one or more bacterial strains comprising16S rDNA sequences of at least 97% homology to SEQ ID NO:12, SEQ IDNO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ IDNO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ IDNO:23, SEQ ID NO:24, SEQ ID NO:25, or SEQ ID NO:26. In some embodimentsof the compositions provided herein, the purified bacterial mixturecomprises at least 2, at least 3, at least 4, at least 5, at least 6, atleast 7, at least 8, at least 9, at least 10, at least 11, at least 12,at least 13, at least 14, or at least 15 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ IDNO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ IDNO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, or SEQ ID NO:26. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 2, at least 3, at least 4, at least5, at least 6, at least 7, at least 8, at least 9, at least 10, at least11, at least 12, at least 13, at least 14, or at least 15 bacterialstrains. In one aspect, the disclosure provides compositions comprisinga purified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% homology to SEQ ID NO:12,SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17,SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22,SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, or SEQ ID NO:26. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 3, at least 4, at least 5, at least 6, atleast 7, at least 8, at least 9, at least 10, at least 11, at least 12,at least 13, at least 14, or at least 15 bacterial strains. In oneaspect, the disclosure provides compositions comprising a purifiedbacterial mixture comprising two or more bacterial strains comprising16S rDNA sequences of at least 97% sequence identity with SEQ ID NO:12,SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17,SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22,SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, or SEQ ID NO:26. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 3, at least 4, at least 5, at least 6, atleast 7, at least 8, at least 9, at least 10, at least 11, at least 12,at least 13, at least 14, or at least 15 bacterial strains.

In one aspect, the disclosure provides compositions comprising one ormore bacterial strains comprising 16S rDNA sequences of at least 97%homology to SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, or SEQID NO:21. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 2, at least 3, at least 4,at least 5, at least 6, at least 7, at least 8, at least 9, or at least10 bacterial strains. In one aspect, the disclosure providescompositions comprising one or more bacterial strains comprising 16SrDNA sequences of at least 97% sequence identity with SEQ ID NO:12, SEQID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ IDNO:18, SEQ ID NO:19, SEQ ID NO:20, or SEQ ID NO:21. In some embodimentsof the compositions provided herein, the purified bacterial mixturecomprises at least 2, at least 3, at least 4, at least 5, at least 6, atleast 7, at least 8, at least 9, or at least 10 bacterial strains. Inone aspect, the disclosure provides compositions comprising two or morebacterial strains comprising 16S rDNA sequences of at least 97% homologyto SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16,SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, or SEQ ID NO:21.In some embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, at least 7, at least 8, at least 9, or at least 10 bacterial strains.

In one aspect, the disclosure provides compositions comprising two ormore bacterial strains comprising 16S rDNA sequences of at least 97%sequence identity with SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ IDNO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ IDNO:20, or SEQ ID NO:21. In some embodiments of the compositions providedherein, the purified bacterial mixture comprises at least 3, at least 4,at least 5, at least 6, at least 7, at least 8, at least 9, or at least10 bacterial strains. In one aspect, the disclosure providescompositions comprising a purified bacterial mixture comprising one ormore bacterial strains comprising 16S rDNA sequences of at least 97%homology to SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:5, or SEQ ID NO:10. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 2, at least 3, or at least 4bacterial strains. In one aspect, the disclosure provides compositionscomprising a purified bacterial mixture comprising one or more bacterialstrains comprising 16S rDNA sequences of at least 97% sequence identitywith SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:5, or SEQ ID NO:10. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 2, at least 3, or at least 4 bacterialstrains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% homology to SEQ ID NO:1,SEQ ID NO:2, SEQ ID NO:5, or SEQ ID NO:10. In some embodiments of thecompositions provided herein, the purified bacterial mixture comprisesat least 3, or at least 4 bacterial strains. In one aspect, thedisclosure provides compositions comprising a purified bacterial mixturecomprising two or more bacterial strains comprising 16S rDNA sequencesof at least 97% sequence identity with SEQ ID NO:1, SEQ ID NO:2, SEQ IDNO:5, or SEQ ID NO:10. In some embodiments of the compositions providedherein, the purified bacterial mixture comprises at least 3, or at least4 bacterial strains. In one aspect, the disclosure provides compositionscomprising a purified bacterial mixture comprising one or more bacterialstrains comprising 16S rDNA sequences of at least 97% homology to SEQ IDNO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9,or SEQ ID NO:11. In some embodiments of the compositions providedherein, the purified bacterial mixture comprises at least 2, at least 3,at least 4, at least 5, at least 6, or at least 7 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ IDNO:9, or SEQ ID NO:11. In some embodiments of the compositions providedherein, the purified bacterial mixture comprises at least 2, at least 3,at least 4, at least 5, at least 6, or at least 7 bacterial strains. Inone aspect, the disclosure provides compositions comprising a purifiedbacterial mixture comprising two or more bacterial strains comprising16S rDNA sequences of at least 97% homology to SEQ ID NO:3, SEQ ID NO:4,SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, or SEQ ID NO:11. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, or at least 7 bacterial strains. In one aspect, the disclosureprovides compositions comprising a purified bacterial mixture comprisingtwo or more bacterial strains comprising 16S rDNA sequences of at least97% sequence identity with SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:6, SEQ IDNO:7, SEQ ID NO:8, SEQ ID NO:9, or SEQ ID NO:11. In some embodiments ofthe compositions provided herein, the purified bacterial mixturecomprises at least 3, at least 4, at least 5, at least 6, or at least 7bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 97% homology to SEQ ID NO:27,SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32,SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37,SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42,SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47,SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.In some embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 2, at least 3, at least 4, at least5, at least 6, at least 7, at least 8, at least 9, at least 10, at least11, at least 12, at least 13, at least 14, at least 15, at least 16, atleast 17, at least 18, at least 19, at least 20, at least 21, at least22, at least 23, at least 24, at least 25, or at least 26 bacterialstrains. In one aspect, the disclosure provides compositions comprisinga purified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ IDNO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ IDNO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ IDNO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ IDNO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ IDNO:52. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 2, at least 3, at least 4,at least 5, at least 6, at least 7, at least 8, at least 9, at least 10,at least 11, at least 12, at least 13, at least 14, at least 15, atleast 16, at least 17, at least 18, at least 19, at least 20, at least21, at least 22, at least 23, at least 24, at least 25, or at least 26bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% homology to SEQ ID NO:27,SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32,SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37,SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42,SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47,SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.In some embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, at least 7, at least 8, at least 9, at least 10, at least 11, atleast 12, at least 13, at least 14, at least 15, at least 16, at least17, at least 18, at least 19, at least 20, at least 21, at least 22, atleast 23, at least 24, at least 25, or at least 26 bacterial strains. Inone aspect, the disclosure provides compositions comprising a purifiedbacterial mixture comprising two or more bacterial strains comprising16S rDNA sequences of at least 97% sequence identity with SEQ ID NO:27,SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32,SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37,SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42,SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47,SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52.In some embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, at least 7, at least 8, at least 9, at least 10, at least 11, atleast 12, at least 13, at least 14, at least 15, at least 16, at least17, at least 18, at least 19, at least 20, at least 21, at least 22, atleast 23, at least 24, at least 25, or at least 26 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 97% homology to SEQ ID NO:27,SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32,SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37,SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42,SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, or SEQ ID NO:47.In some embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 2, least 3, at least 4, at least 5,at least 6, at least 7, at least 8, at least 9, at least 10, at least11, at least 12, at least 13, at least 14, at least 15, at least 16, atleast 17, at least 18, at least 19, at least 20, or at least 21bacterial strains. In one aspect, the disclosure provides compositionscomprising a purified bacterial mixture comprising one or more bacterialstrains comprising 16S rDNA sequences of at least 97% sequence identitywith SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ IDNO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ IDNO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ IDNO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ IDNO:46, or SEQ ID NO:47. In some embodiments of the compositions providedherein, the purified bacterial mixture comprises at least 2, least 3, atleast 4, at least 5, at least 6, at least 7, at least 8, at least 9, atleast 10, at least 11, at least 12, at least 13, at least 14, at least15, at least 16, at least 17, at least 18, at least 19, at least 20, orat least 21 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% homology to SEQ ID NO:27,SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32,SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37,SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42,SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, or SEQ ID NO:47.In some embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, at least 7, at least 8, at least 9, at least 10, at least 11, atleast 12, at least 13, at least 14, at least 15, at least 16, at least17, at least 18, at least 19, at least 20, or at least 21 bacterialstrains. In one aspect, the disclosure provides compositions comprisinga purified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ IDNO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ IDNO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ IDNO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, or SEQ IDNO:47. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 3, at least 4, at least 5,at least 6, at least 7, at least 8, at least 9, at least 10, at least11, at least 12, at least 13, at least 14, at least 15, at least 16, atleast 17, at least 18, at least 19, at least 20, or at least 21bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 97% homology to SEQ ID NO:27,SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32,SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, or SEQ ID NO:37.In some embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 2, at least 3, at least 4, at least5, at least 6, at least 7, at least 8, at least 9, at least 10, or atleast 11 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ IDNO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, or SEQ IDNO:37. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 2, at least 3, at least 4,at least 5, at least 6, at least 7, at least 8, at least 9, at least 10,or at least 11 bacterial strains. In one aspect, the disclosure providescompositions comprising a purified bacterial mixture comprising two ormore bacterial strains comprising 16S rDNA sequences of at least 97%homology to SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ IDNO:36, or SEQ ID NO:37. In some embodiments of the compositions providedherein, the purified bacterial mixture comprises at least 3, at least 4,at least 5, at least 6, at least 7, at least 8, at least 9, at least 10,or at least 11 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ IDNO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, or SEQ IDNO:37. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 3, at least 4, at least 5,at least 6, at least 7, at least 8, at least 9, at least 10, or at least11 bacterial strains. In one aspect, the disclosure providescompositions comprising a purified bacterial mixture comprising one ormore bacterial strains comprising 16S rDNA sequences of at least 97%homology to SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ IDNO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ IDNO:52. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 2, at least 3, at least 4,at least 5, at least 6, at least 7, at least 8, at least 9, at least 10,at least 11, at least 12, at least 13, at least 14, or at least 15bacterial strains. In one aspect, the disclosure provides compositionscomprising a purified bacterial mixture comprising one or more bacterialstrains comprising 16S rDNA sequences of at least 97% sequence identitywith SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ IDNO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ IDNO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ IDNO:52. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 2, at least 3, at least 4,at least 5, at least 6, at least 7, at least 8, at least 9, at least 10,at least 11, at least 12, at least 13, at least 14, or at least 15bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% homology to SEQ ID NO:38,SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43,SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48,SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 3, at least 4, at least 5, at least 6, atleast 7, at least 8, at least 9, at least 10, at least 11, at least 12,at least 13, at least 14, or at least 15 bacterial strains. In oneaspect, the disclosure provides compositions comprising a purifiedbacterial mixture comprising two or more bacterial strains comprising16S rDNA sequences of at least 97% sequence identity with SEQ ID NO:38,SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43,SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48,SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, or SEQ ID NO:52. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 3, at least 4, at least 5, at least 6, atleast 7, at least 8, at least 9, at least 10, at least 11, at least 12,at least 13, at least 14, or at least 15 bacterial strains. In oneaspect, the disclosure provides compositions comprising a purifiedbacterial mixture comprising one or more bacterial strains comprising16S rDNA sequences of at least 97% homology to SEQ ID NO:38, SEQ IDNO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ IDNO:44, SEQ ID NO:45, SEQ ID NO:46, or SEQ ID NO:47. In some embodimentsof the compositions provided herein, the purified bacterial mixturecomprises at least 2, at least 3, at least 4, at least 5, at least 6, atleast 7, at least 8, at least 9, or at least 10 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ IDNO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, or SEQ ID NO:47. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 2, at least 3, at least 4, at least5, at least 6, at least 7, at least 8, at least 9, or at least 10bacterial strains. In one aspect, the disclosure provides compositionscomprising a purified bacterial mixture comprising two or more bacterialstrains comprising 16S rDNA sequences of at least 97% homology to SEQ IDNO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ IDNO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, or SEQ ID NO:47. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, at least 7, at least 8, at least 9, or at least 10 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ IDNO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, or SEQ ID NO:47. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, at least 7, at least 8, at least 9, or at least 10 bacterial strains.In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 97% homology to SEQ ID NO:27,SEQ ID NO:28, SEQ ID NO:31 or SEQ ID NO:36. In some embodiments of thecompositions provided herein, the purified bacterial mixture comprisesat least 2, at least 3, or at least 4 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:27, SEQ ID NO:28, SEQ ID NO:31 or SEQ ID NO:36. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 2, at least 3, or at least 4 bacterialstrains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strainscomprising 16S rDNA sequences of at least 97% homology to SEQ ID NO:27,SEQ ID NO:28, SEQ ID NO:31 or SEQ ID NO:36. In some embodiments of thecompositions provided herein, the purified bacterial mixture comprisesat least 3, or at least 4 bacterial strains. In one aspect, thedisclosure provides compositions comprising a purified bacterial mixturecomprising two or more bacterial strains comprising 16S rDNA sequencesof at least 97% sequence identity with SEQ ID NO:27, SEQ ID NO:28, SEQID NO:31 or SEQ ID NO:36. In some embodiments of the compositionsprovided herein, the purified bacterial mixture comprises at least 3, orat least 4 bacterial strains. In one aspect, the disclosure providescompositions comprising a purified bacterial mixture comprising one ormore bacterial strains comprising 16S rDNA sequences of at least 97%homology to SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:33, SEQID NO:34, SEQ ID NO:35, or SEQ ID NO:37. In some embodiments of thecompositions provided herein, the purified bacterial mixture comprisesat least 2, at least 3, at least 4, at least 5, at least 6, or at least7 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising one or more bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:29, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ IDNO:35, or SEQ ID NO:37. In some embodiments of the compositions providedherein, the purified bacterial mixture comprises at least 2, at least 3,at least 4, at least 5, at least 6, or at least 7 bacterial strains. Inone aspect, the disclosure provides compositions comprising a purifiedbacterial mixture comprising two or more bacterial strains comprising16S rDNA sequences of at least 97% homology to SEQ ID NO:29, SEQ IDNO:30, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, or SEQ IDNO:37. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 3, at least 4, at least 5,at least 6, or at least 7 bacterial strains. In one aspect, thedisclosure provides compositions comprising a purified bacterial mixturecomprising two or more bacterial strains comprising 16S rDNA sequencesof at least 97% sequence identity with SEQ ID NO:29, SEQ ID NO:30, SEQID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:37. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, or at least 7 bacterial strains.

In one aspect, the disclosure provides compositions comprising abacterial strain comprising a 16S rDNA sequence with a nucleic acidsequence selected from the group consisting of SEQ ID NOs:1-26. In oneaspect, the disclosure provides compositions comprising as an activeingredient a bacterial strain comprising a 16S rDNA sequence with anucleic acid sequence selected from the group consisting of SEQ IDNOs:1-26. It should be appreciated that for all compositions providedherein, in some embodiments, the bacterial strain or the bacterialstrains are the active ingredient of the composition. In one aspect, thedisclosure provides compositions comprising a bacterial straincomprising a 16S rDNA sequence with a nucleic acid sequence selectedfrom the group consisting of SEQ ID NOs:1-21. In one aspect, thedisclosure provides compositions comprising as an active ingredient abacterial strain comprising a 16S rDNA sequence with a nucleic acidsequence selected from the group consisting of SEQ ID NOs:1-21. In oneaspect, the disclosure provides compositions comprising a bacterialstrain comprising a 16S rDNA sequence with a nucleic acid sequenceselected from the group consisting of SEQ ID NOs:1-11. In one aspect,the disclosure provides compositions comprising as an active ingredienta bacterial strain comprising a 16S rDNA sequence with a nucleic acidsequence selected from the group consisting of SEQ ID NOs:1-11.

In one aspect, the disclosure provides compositions comprising abacterial strain comprising a 16S rDNA sequence with a nucleic acidsequence selected from the group consisting of SEQ ID NOs:54-64. In oneaspect, the disclosure provides compositions comprising as an activeingredient a bacterial strain comprising a 16S rDNA sequence with anucleic acid sequence selected from the group consisting of SEQ IDNOs:54-64. It should be appreciated that for all compositions providedherein, in some embodiments, the bacterial strains are purified. Thus,for example the disclosure provides purified bacterial strainscomprising a 16S rDNA sequence with a nucleic acid sequence selectedfrom the group consisting of SEQ ID NOs:1-26. In addition, for example,the disclosure provides compositions comprising purified bacterialstrains comprising a 16S rDNA sequence with a nucleic acid sequenceselected from the group consisting of SEQ ID NOs:1-26. The bacterialstrains disclosed herein originally may have been obtained and purifiedfrom the microbiota of one or more human individuals or obtained fromsources other than the human microbiota, including soil and non-humanmicrobiota. As provided herein, in some embodiments, bacteria isolatedfrom the human microbiota, non-human microbiota, soil, or anyalternative source are purified prior to use in the compositions andmethods provided herein.

In one aspect, the disclosure provides compositions comprising one ormore bacterial strains, wherein the one or more bacterial strainscomprise a 16S rDNA sequence with a nucleic acid sequence selected fromthe group consisting of SEQ ID NOs:1-26. In one aspect, the disclosureprovides compositions comprising one or more bacterial strains whereinthe one or more bacterial strains comprise 16S rDNA sequences having atleast 97% homology with nucleic acid sequences selected from the groupconsisting of SEQ ID NOs:1-26. As discussed previously, in someembodiments, the bacterial strains are purified. Thus, in one aspect,the disclosure provides compositions comprising one or more purifiedbacterial strains wherein the one or more purified bacterial strainscomprise 16S rDNA sequences having at least 97% homology with nucleicacid sequences selected from the group consisting of SEQ ID NOs:1-26. Inone aspect, the disclosure provides compositions comprising one or morebacterial strains wherein the one or more bacterial strains comprise 16SrDNA sequences having at least 97% sequence identity with nucleic acidsequences selected from the group consisting of SEQ ID NOs:1-26. Asdiscussed previously, in some embodiments, the bacterial strains arepurified. Thus, in one aspect, the disclosure provides compositionscomprising one or more purified bacterial strains wherein the one ormore purified bacterial strains comprise 16S rDNA sequences having atleast 97% sequence identity with nucleic acid sequences selected fromthe group consisting of SEQ ID NOs:1-26.

In one aspect, the disclosure provides compositions comprising two ormore purified bacterial strains wherein the two or more purifiedbacterial strains comprise 16S rDNA sequences having at least 97%homology with nucleic acid sequences selected from the group consistingof SEQ ID NOs:1-26. As discussed above, in some embodiments, thebacterial strains are the active ingredient of the composition. Thus, insome embodiments, the disclosure provides compositions comprising as anactive ingredient two or more purified bacterial strains wherein the twoor more purified bacterial strains comprise 16S rDNA sequences having atleast 97% homology with nucleic acid sequences selected from the groupconsisting of SEQ ID NOs:1-26. In one aspect, the disclosure providescompositions comprising two or more purified bacterial strains whereinthe two or more purified bacterial strains comprise 16S rDNA sequenceshaving at least 97% sequence identity with nucleic acid sequencesselected from the group consisting of SEQ ID NOs:1-26. As discussedabove, in some embodiments, the bacterial strains are the activeingredient of the composition. Thus, in some embodiments, the disclosureprovides compositions comprising as an active ingredient two or morepurified bacterial strains wherein the two or more purified bacterialstrains comprise 16S rDNA sequences having at least 97% sequenceidentity with nucleic acid sequences selected from the group consistingof SEQ ID NOs:1-26.

In one aspect, the disclosure provides bacterial strains andcombinations of bacterial strains that are homologous or have a highpercent of homology with bacterial strains comprising 16S rDNA sequencesselected from the group consisting of SEQ ID NOs:1-26. As discussedpreviously, in some embodiments, the bacterial strains are purified. Thebacterial strains disclosed herein that have a 16S rDNA sequence with anucleic acid sequence selected from the group consisting of SEQ IDNOs:1-26 have a high percent of homology (e.g., greater than 90%) orsequence identity, with 16S rDNA sequences of bacterial strains thathave been described in various databases (See e.g., the National Centerfor Biotechnology Information). Table 1 provides the closest knownspecies by homology when the 16S rDNA sequences comprising SEQ IDNOs:1-26 are compared to 16S rDNA sequences of bacterial speciesavailable in public databases.

By way of example, the bacterial strain comprising a 16S rDNA sequencewith SEQ ID NO:1 disclosed herein has the highest homology with abacterial strain of the species Phascolarctobacterium faecium as definedby NCBI Accession # LN998073 (having 16S rDNA sequence SEQ ID NO:27).While the bacterial strain with SEQ ID NO:1 has homology with otherpublished bacterial strains as well, the highest homology is with abacterial strain of the species Phascolarctobacterium faecium as definedby NCBI Accession # LN998073. It should be appreciated that multiplebacterial strains disclosed herein may have the highest homology withthe same species.

It should further be appreciated that the bacterial strains disclosedherein that have a 16S rDNA sequence with a nucleic acid sequenceselected from the group consisting of SEQ ID NOs:1-26, are alsohomologous to other strains based on their whole genome sequence, orsubset of their whole genome sequence.

Thus, it should be appreciated that, in one aspect, the disclosure alsoprovides compositions and methods comprising bacterial species withclose homology to the bacterial strains that have a 16S rDNA sequencewith a nucleic acid sequence selected from the group consisting of SEQID NOs:1-26.

In one aspect, the disclosure provides compositions comprising one ormore bacterial strains wherein the one or more bacterial strains are ofspecies selected from the group consisting of Phascolarctobacteriumfaecium, Fusobacterium ulcerans, Bacteroides dorei, Bacteroidesuniformis, Subdoligranulum sp., Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes sp., Parabacteroides gordonii,Eubacterum limosum, Parabacteroides distasonis, Bacteroidescellulosilyticus, Bacteroides clarus, Anaerostipes caccae, Bacteroidessalyersiae, Bacteroides fragilis, Bacteroides uniformis, Bacteroideseggerthii, Clostridium sp., Parabacteroides goldsteinii, Bacteroidessp., Lachnospiraceae bacterium HGA0140, Hungatella hathewayi,Clostridium lavalense, Ruminococcus sp., and Clostridium innocuum In oneaspect, the disclosure provides compositions comprising one or morebacterial strains wherein the one or more bacterial strains are ofspecies selected from the group consisting of Phascolarctobacteriumfaecium, Fusobacterium ulcerans, Bacteroides dorei, Bacteroidesuniformis, Subdoligranulum sp., Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes sp., Parabacteroides gordonii,Eubacterum limosum, Parabacteroides distasonis, Bacteroidescellulosilyticus, Bacteroides clarus, Anaerostipes caccae, Bacteroidessalyersiae, Bacteroides fragilis; Bacteroides uniformis, Bacteroideseggerthii, Clostridium sp., Parabacteroides goldsteinii, and Bacteroidessp.

In one aspect, the disclosure provides compositions comprising one ormore bacterial strains wherein the one or more bacterial strains are ofspecies selected from the group consisting of Phascolarctobacteriumfaecium, Fusobacterium ulcerans, Bacteroides dorei, Bacteroidesuniformis, Subdoligranulum sp., Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes sp., Parabacteroides gordonii,Eubacterum limosum, and Parabacteroides distasonis. In one aspect, thedisclosure provides compositions comprising one or more bacterialstrains wherein the one or more bacterial strains are of speciesselected from the group consisting of Bacteroides cellulosilyticus,Bacteroides clarus, Anaerostipes caccae, Bacteroides salyersiae,Bacteroides fragilis, Bacteroides uniformis, Bacteroides eggerthii,Clostridium sp., Parabacteroides goldsteinii, Bacteroides sp.,Lachnospiraceae bacterium HGA0140, Hungatella hathewayi, Clostridiumlavalense, Ruminococcus sp., and Clostridium innocuum. In one aspect,the disclosure provides compositions comprising one or more bacterialstrains wherein the one or more bacterial strains are of speciesselected from the group consisting of Bacteroides cellulosilyticus,Bacteroides clarus, Anaerostipes caccae, Bacteroides salyersiae,Bacteroides fragilis, Bacteroides uniformis, Bacteroides eggerthii,Clostridium sp., Parabacteroides goldsteinii, and Bacteroides sp.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strains ofspecies selected from the group consisting of Phascolarctobacteriumfaecium, Fusobacterium ulcerans, Bacteroides dorei, Bacteroidesuniformis, Subdoligranulum sp., Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes sp., Parabacteroides gordonii,Eubacterum limosum, Parabacteroides distasonis, Bacteroidescellulosilyticus, Bacteroides clarus, Anaerostipes caccae, Bacteroidessalyersiae, Bacteroides fragilis, Bacteroides uniformis, Bacteroideseggerthii, Clostridium sp., Parabacteroides goldsteinii, Bacteroidessp., Lachnospiraceae bacterium HGA0140, Hungatella hathewayi,Clostridium lavalense, Ruminococcus sp., and Clostridium innocuum. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, at least 7, at least 8, at least 9, at least 10, at least 11, atleast 12, at least 13, at least 14, at least 15, at least 16, at least17, at least 18, at least 19, at least 20, at least 21, at least 22, atleast 23, at least 24, at least 25, or at least 26 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strains ofspecies selected from the group consisting of Phascolarctobacteriumfaecium, Fusobacterium ulcerans, Bacteroides dorei, Bacteroidesuniformis, Subdoligranulum sp., Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes sp., Parabacteroides gordonii,Eubacterum limosum, Parabacteroides distasonis, Bacteroidescellulosilyticus, Bacteroides clarus, Anaerostipes caccae, Bacteroidessalyersiae, Bacteroides fragilis, Bacteroides uniformis, Bacteroideseggerthii, Clostridium sp., Parabacteroides goldsteinii, and Bacteroidessp. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 3, at least 4, at least 5,at least 6, at least 7, at least 8, at least 9, at least 10, at least11, at least 12, at least 13, at least 14, at least 15, at least 16, atleast 17, at least 18, at least 19, at least 20, or at least 21bacterial strains. In one aspect, the disclosure provides compositionscomprising a purified bacterial mixture comprising two or more bacterialstrains of species selected from the group consisting ofPhascolarctobacterium faecium, Fusobacterium ulcerans, Bacteroidesdorei, Bacteroides uniformis, Subdoligranulum sp., Paraprevotellaxylaniphila, Parabacteroides johnsonii, Alistipes sp., Parabacteroidesgordonii, Eubacterum limosum, and Parabacteroides distasonis. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 3, at least 4, at least 5, at least 6, atleast 7, at least 8, at least 9, at least 10, or at least 11 bacterialstrains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising Phascolarctobacterium faecium,Fusobacterium ulcerans, Bacteroides dorei, Bacteroides uniformis,Subdoligranulum sp., Paraprevotella xylaniphila, Parabacteroidesjohnsonii, Alistipes sp., Parabacteroides gordonii, Eubacterum limosum,and Parabacteroides distasonis. In one aspect, the disclosure providescompositions comprising a purified bacterial mixture consisting ofPhascolarctobacterium faecium, Fusobacterium ulcerans, Bacteroidesdorei, Bacteroides uniformis, Subdoligranulum sp., Paraprevotellaxylaniphila, Parabacteroides johnsonii, Alistipes sp., Parabacteroidesgordonii, Eubacterum limosum, and Parabacteroides distasonis. In oneaspect, the disclosure provides compositions comprising a purifiedbacterial mixture comprising one or more bacterial strains of speciesselected from the group consisting of Phascolarctobacterium faecium,Phascolarctobacterium sp. CAG:207, Fusobacterium ulcerans, Fusobacteriumvarium, Bacteroides dorei, Bacteroides fluxus, Bacteroides uniformis,Bacteroides sp. D20 Subdoligranulum sp., Ruthenibacteriumlactatiformans, Ruminococcaceae bacterium cv2, Gemminger formicilis,Paraprevotella xylaniphila, Parabacteroides johnsonii, Alistipes sp.,Alistipes senegalesis, Parabacteroides gordonii, Parabacteroides sp.HGS0025, Eubacterum limosum, Parabacteroides sp. CAG:2 andParabacteroides distasonis. In some embodiments of the compositionsprovided herein, the purified bacterial mixture comprises at least 2, atleast 3, at least 4, at least 5, at least 6, at least 7, at least 8, atleast 9, at least 10, or at least 11 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising:

1) Phascolarctobacterium faecium, or Phascolarctobacterium sp. CAG:207;

2) Fusobacterium ulcerans, or Fusobacterium varium;

3) Bacteroides dorei, or Bacteroides fluxus,

4) Bacteroides uniformis, or Bacteroides sp. D20,

5) Subdoligranulum sp., Ruthenibacterium lactatiformans, Ruminococcaceaebacterium cv2, or Gemminger formicilis,

6) Paraprevotella xylaniphila,

7) Parabacteroides johnsonii,

8) Alistipes sp., Alistipes timonensis, or Alistipes senegalesis,

9) Parabacteroides gordonii, or Parabacteroides sp. HGS0025,

10) Eubacterum limosum, and

11) Parabacteroides sp. CAG:2 or Parabacteroides distasonis.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture consisting of:

1) Phascolarctobacterium faecium, or Phascolarctobacterium sp. CAG:207;

2) Fusobacterium ulcerans, or Fusobacterium varium;

3) Bacteroides dorei, or Bacteroides fluxus,

4) Bacteroides uniformis, or Bacteroides sp. D20,

5) Subdoligranulum sp., Ruthenibacterium lactatiformans, Ruminococcaceaebacterium cv2, or Gemminger formicilis,

6) Paraprevotella xylaniphila,

7) Parabacteroides johnsonii,

8) Alistipes sp., Alistipes timonensis, or Alistipes senegalesis,

9) Parabacteroides gordonii, or Parabacteroides sp. HGS0025,

10) Eubacterum limosum, and

11) Parabacteroides sp. CAG:2 or Parabacteroides distasonis. In oneaspect, the disclosure provides compositions comprising a purifiedbacterial mixture comprising one or more bacterial strains of speciesselected from the group consisting of Phascolarctobacterium faecium,Fusobacterium varium, Bacteroides dorei, Bacteroides uniformis,Ruthenibacterium lactatiformans, Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes senegalesis, Parabacteroidesgordonii, Eubacterum limosum, and Parabacteroides distasonis. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 2, at least 3, at least 4, at least 5, atleast 6, at least 7, at least 8, at least 9, at least 10, or at least 11bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising Phascolarctobacterium faecium,Fusobacterium varium, Bacteroides dorei, Bacteroides uniformis,Ruthenibacterium lactatiformans, Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes senegalesis, Parabacteroidesgordonii, Eubacterum limosum, and Parabacteroides distasonis.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture consisting of Phascolarctobacterium faecium,Fusobacterium varium, Bacteroides dorei, Bacteroides uniformis,Ruthenibacterium lactatiformans, Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes senegalesis, Parabacteroidesgordonii, Eubacterum limosum, and Parabacteroides distasonis. In oneaspect, the disclosure provides compositions comprising a purifiedbacterial mixture comprising one or more bacterial strains of speciesselected from the group consisting of Phascolarctobacterium sp. CAG:207,Fusobacterium ulcerans, Bacteroides dorei, Bacteroides sp. D20,Ruminococcaceae bacterium cv2, Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes senegalesis, Parabacteroides sp.HGS0025, Eubacterum limosum, and Parabacteroides sp. CAG:2. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 2, at least 3, at least 4, at least 5, atleast 6, at least 7, at least 8, at least 9, at least 10, or at least 11bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising Phascolarctobacterium sp. CAG:207,Fusobacterium ulcerans, Bacteroides dorei, Bacteroides sp. D20,Ruminococcaceae bacterium cv2, Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes senegalesis, Parabacteroides sp.HGS0025, Eubacterum limosum, and Parabacteroides sp. CAG:2. In oneaspect, the disclosure provides compositions comprising a purifiedbacterial mixture consisting of Phascolarctobacterium sp. CAG:207,Fusobacterium ulcerans, Bacteroides dorei, Bacteroides sp. D20,Ruminococcaceae bacterium cv2, Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes senegalesis, Parabacteroides sp.HGS0025, Eubacterum limosum, and Parabacteroides sp. CAG:2. In oneaspect, the disclosure provides compositions comprising a purifiedbacterial mixture comprising two or more bacterial strains of speciesselected from the group consisting of Phascolarctobacterium faecium,Phascolarctobacterium sp. CAG:207, Fusobacterium ulcerans, Fusobacteriumvarium, Bacteroides dorei, Bacteroides fluxus, Bacteroides uniformis,Bacteroides sp. D20 Subdoligranulum sp., Ruthenibacteriumlactatiformans, Ruminococcaceae bacterium cv2, Gemminger formicilis,Paraprevotella xylaniphila, Parabacteroides johnsonii, Alistipes sp.,Alistipes timonensis, Alistipes senegalesis, Parabacteroides gordonii,Parabacteroides sp. HGS0025, Eubacterum limosum, Parabacteroides sp.CAG:2 and Parabacteroides distasonis. In some embodiments of thecompositions provided herein, the purified bacterial mixture comprises,at least 3, at least 4, at least 5, at least 6, at least 7, at least 8,at least 9, at least 10, or at least 11 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strains ofspecies selected from the group consisting of Phascolarctobacteriumfaecium, Fusobacterium varium, Bacteroides dorei, Bacteroides uniformis,Ruthenibacterium lactatiformans, Paraprevotella xylaniphila,Parabacteroides johnsonii, Alistipes senegalesis, Parabacteroidesgordonii, Eubacterum limosum, and Parabacteroides distasonis. In someembodiments of the compositions provided herein, the purified bacterialmixture comprises at least 2, at least 3, at least 4, at least 5, atleast 6, at least 7, at least 8, at least 9, at least 10, or at least 11bacterial strains. In one aspect, the disclosure provides compositionscomprising a purified bacterial mixture comprising two or more bacterialstrains of species selected from the group consisting ofPhascolarctobacterium sp. CAG:207, Fusobacterium ulcerans, Bacteroidesdorei, Bacteroides sp. D20, Ruminococcaceae bacterium cv2,Paraprevotella xylaniphila, Parabacteroides johnsonii, Alistipessenegalesis, Parabacteroides sp. HGS0025, Eubacterum limosum, andParabacteroides sp. CAG:2. In some embodiments of the compositionsprovided herein, the purified bacterial mixture comprises at least 2, atleast 3, at least 4, at least 5, at least 6, at least 7, at least 8, atleast 9, at least 10, or at least 11 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strains ofspecies selected from the group consisting of Bacteroidescellulosilyticus, Bacteroides clarus, Anaerostipes caccae, Bacteroidessalyersiae, Bacteroides fragilis, Bacteroides uniformis, Bacteroideseggerthii, Clostridium sp., Parabacteroides goldsteinii, Bacteroidessp., Lachnospiraceae bacterium HGA0140, Hungatella hathewayi,Clostridium lavalense, Ruminococcus sp., and Clostridium innocuum. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, at least 7, at least 8, at least 9, at least 10, at least 11, atleast 12, at least 13, at least 14, or at least 15 bacterial strains. Inone aspect, the disclosure provides compositions comprising a purifiedbacterial mixture comprising two or more bacterial strains of speciesselected from the group consisting of Bacteroides cellulosilyticus,Bacteroides clarus, Anaerostipes caccae, Bacteroides salyersiae,Bacteroides fragilis, Bacteroides uniformis, Bacteroides eggerthii,Clostridium sp., Parabacteroides goldsteinii, and Bacteroides sp. Insome embodiments of the compositions provided herein, the purifiedbacterial mixture comprises at least 3, at least 4, at least 5, at least6, at least 7, at least 8, at least 9, or at least 10 bacterial strains.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising two or more bacterial strains ofspecies selected from the group consisting of Phascolarctobacteriumfaecium, Fusobacterium ulcerans, Subdoligranulum sp., and Eubacterumlimosum. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises at least 3, or at least 4 bacterialstrains. In one aspect, the disclosure provides compositions comprisinga purified bacterial mixture comprising two or more bacterial strains ofspecies selected from the group consisting of Bacteroides dorei,Bacteroides uniformis, Paraprevotella xylaniphila, Parabacteroidesjohnsonii, Alistipes sp., Parabacteroides gordonii, and Parabacteroidesdistasonis. In some embodiments of the compositions provided herein, thepurified bacterial mixture comprises, at least 3, at least 4, at least5, at least 6, or at least 7 bacterial strains. It should be appreciatedthat the compositions may include multiple strains of a particularspecies. Thus, for illustration, a non-limiting example of thecompositions disclosed herein, comprises one strain of Bacteroidessalyersiae and two strains of Bacteroides uniformis. The disclosureprovides also encompasses compositions comprising bacterial strains thatare close in homology to and/or fall within the speciesPhascolarctobacterium faecium, Fusobacterium ulcerans, Bacteroidesdorei, Bacteroides uniformis, Subdoligranulum sp., Paraprevotellaxylaniphila, Parabacteroides johnsonii, Alistipes sp., Parabacteroidesgordonii, Eubacterum limosum, Parabacteroides distasonis, Bacteroidescellulosilyticus, Bacteroides clarus, Anaerostipes caccae, Bacteroidessalyersiae, Bacteroides fragilis, Bacteroides uniformis, Bacteroideseggerthii, Clostridium sp., Parabacteroides goldsteinii, Bacteroidessp., Lachnospiraceae bacterium HGA0140, Hungatella hathewayi,Clostridium lavalense, Ruminococcus sp., and Clostridium innocuum.

Thus, in one embodiment, the compositions of the disclosure include oneor more bacterial strains comprising 16S rDNA sequences having at least97% homology with nucleic acid sequences selected from the groupconsisting of SEQ ID NOs:27-52. In some embodiments, the compositions ofthe disclosure include two or more bacterial strains comprising 16S rDNAsequences having at least 97% homology with nucleic acid sequencesselected from the group consisting of SEQ ID NOs:27-52. Thus, in oneembodiment, the compositions of the disclosure include one or morebacterial strains comprising 16S rDNA sequences having at least 97%sequence identity with nucleic acid sequences selected from the groupconsisting of SEQ ID NOs:27-52. In some embodiments, the compositions ofthe disclosure include two or more bacterial strains comprising 16S rDNAsequences having at least 97% sequence identity with nucleic acidsequences selected from the group consisting of SEQ ID NOs:27-52.

In one aspect, the compositions of the disclosure include two or morepurified bacterial strains comprising 16S rDNA sequences having at least97% homology with nucleic acid sequences selected from the groupconsisting of SEQ ID NOs:1-26. In some embodiments, the compositions ofthe disclosure include two or more purified bacterial strains comprising16S rDNA sequences having at least 97% sequence identity with nucleicacid sequences selected from the group consisting of SEQ ID NOs:1-26. Insome embodiments, the compositions of the disclosure include two or morebacterial strains of species selected from the group consisting ofPhascolarctobacterium faecium, Fusobacterium ulcerans, Bacteroidesdorei, Bacteroides uniformis, Subdoligranulum sp., Paraprevotellaxylaniphila, Parabacteroides johnsonii, Alistipes sp., Parabacteroidesgordonii, Eubacterum limosum, Parabacteroides distasonis, Bacteroidescellulosilyticus, Bacteroides clarus, Anaerostipes caccae, Bacteroidessalyersiae, Bacteroides fragilis, Bacteroides uniformis, Bacteroideseggerthii, Clostridium sp., Parabacteroides goldsteinii, Bacteroidessp., Lachnospiraceae bacterium HGA0140, Hungatella hathewayi,Clostridium lavalense, Ruminococcus sp., and Clostridium innocuum. Insome embodiments, the compositions of the disclosure include two or morepurified bacterial strains comprising 16S rDNA sequences having at least97% homology with nucleic acid sequences selected from the groupconsisting of SEQ ID NO:27-52. In some embodiments, the compositions ofthe disclosure include two or more purified bacterial strains comprising16S rDNA sequences having at least 97% sequence identity with nucleicacid sequences selected from the group consisting of SEQ ID NO:27-52.

In some embodiments, the disclosure provides compositions with two ormore purified bacterial strains that comprise 16S rDNA sequences withnucleic acid sequences selected from the group consisting of SEQ IDNOs:1-26. In some embodiments, the disclosure provides compositions withfive or more purified bacterial strains that comprise 16S rDNA sequenceswith nucleic acid sequences selected from the group consisting of SEQ IDNOs:1-26. In some embodiments, the disclosure provides compositions withat least ten purified bacterial strains, wherein the bacterial strainscomprise 16S rDNA sequences with nucleic acid sequences SEQ ID NOs:1-26,respectively. In some embodiments, the disclosure provides a compositionconsisting of ten purified bacterial strains, wherein the bacterialstrains comprise 16S rDNA sequences with nucleic acid sequences SEQ IDNOs:1-26, respectively. In some embodiments, the disclosure provides acomposition essentially consisting of eleven purified bacterial strains,wherein the bacterial strains comprise 16S rDNA sequences with nucleicacid sequences SEQ ID NOs:1-26, respectively. As used herein,essentially consisting of refers to a composition that includes noadditional bacterial strains.

In some embodiments, the disclosure provides compositions with bacterialstrains that comprise 16S rDNA sequences having at least 97% homologywith nucleic acid sequences selected from the group consisting of: SEQID NOs:1-26. In some embodiments, the disclosure provides compositionswith two or more purified bacterial strains that comprise 16S rDNAsequences having at least 97% homology with nucleic acid sequencesselected from the group consisting of SEQ ID NOs:1-26. In someembodiments, the disclosure provides compositions with five or morepurified bacterial strains that comprise 16S rDNA having at least 97%homology with nucleic acid sequences selected from the group consistingof SEQ ID NOs:1-26. In some embodiments, the disclosure providescompositions with at least ten purified bacterial strains, wherein thebacterial strains comprise 16S rDNA sequences having at least 97%homology with nucleic acid sequences SEQ ID NOs:1-26, respectively. Insome embodiments, the disclosure provides a composition consisting often purified bacterial strains, wherein the bacterial strains comprise16S rDNA sequences having at least 97% homology with nucleic acidsequences SEQ ID NOs:1-26, respectively. In some embodiments, thedisclosure provides a composition essentially consisting of ten purifiedbacterial strains, wherein the bacterial strains comprise 16S rDNAsequences having at least 97% homology with nucleic acid sequences SEQID NOs:1-26, respectively.

In some embodiments, the disclosure provides compositions with bacterialstrains that comprise 16S rDNA sequences having at least 97% sequenceidentity with nucleic acid sequences selected from the group consistingof: SEQ ID NOs:1-26. In some embodiments, the disclosure providescompositions with two or more purified bacterial strains that comprise16S rDNA sequences having at least 97% sequence identity with nucleicacid sequences selected from the group consisting of SEQ ID NOs:1-26. Insome embodiments, the disclosure provides compositions with five or morepurified bacterial strains that comprise 16S rDNA having at least 97%sequence identity with nucleic acid sequences selected from the groupconsisting of SEQ ID NOs:1-26. In some embodiments, the disclosureprovides compositions with at least ten purified bacterial strains,wherein the bacterial strains comprise 16S rDNA sequences having atleast 97% sequence identity with nucleic acid sequences SEQ ID NOs:1-26,respectively. In some embodiments, the disclosure provides a compositionconsisting of ten purified bacterial strains, wherein the bacterialstrains comprise 16S rDNA sequences having at least 97% sequenceidentity with nucleic acid sequences SEQ ID NOs:1-26, respectively. Insome embodiments, the disclosure provides a composition essentiallyconsisting of ten purified bacterial strains, wherein the bacterialstrains comprise 16S rDNA sequences having at least 97% sequenceidentity with nucleic acid sequences SEQ ID NOs:1-26, respectively.

In one aspect, the disclosure provides a composition comprisingbacterial strains that are related to the following bacterial species:Phascolarctobacterium faecium, Fusobacterium ulcerans, Bacteroidesdorei, Bacteroides uniformis, Subdoligranulum sp., Paraprevotellaxylaniphila, Parabacteroides johnsonii, Alistipes sp., Parabacteroidesgordonii, Eubacterum limosum, Parabacteroides distasonis, Bacteroidescellulosilyticus, Bacteroides clarus, Anaerostipes caccae, Bacteroidessalyersiae, Bacteroides fragilis, Bacteroides uniformis, Bacteroideseggerthii, Clostridium sp., Parabacteroides goldsteinii, Bacteroidessp., Lachnospiraceae bacterium HGA0140, Hungatella hathewayi,Clostridium lavalense, Ruminococcus sp., and Clostridium innocuum (Seee.g., Table 1). It should be appreciated that multiple bacterial strainsof the compositions disclosed herein can have the same related bacterialspecies. In some embodiments, the disclosure provides compositions withtwo or more purified bacterial strains comprising 16S rDNA sequenceshaving at least 97% homology with nucleic acid sequences selected fromthe group consisting of SEQ ID NO:27-52. In some embodiments, thedisclosure provides compositions with two or more purified bacterialstrains comprising 16S rDNA sequences having at least 97% sequenceidentity with nucleic acid sequences selected from the group consistingof SEQ ID NO:27-52.

In one aspect, the disclosure provides bacterial strains with 16S rDNAsequences that have homology to a nucleic acid sequence of any one ofthe sequences of the bacterial strains or species described herein. Insome embodiments, the bacterial strain has at least 60%, at least 70%,at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, atleast 85%, at least 86%, at least 87%, at least 88%, at least 89%, atleast 90%, at least 91%, at least 92%, at least 93%, at least 94%, atleast 95%, at least 96%, at least 97%, at least 98%, at least 99%, atleast 99.5%, at least 99.6%, at least 99.7%, at least 99.8%, at least99.9%, or up to 100% homology relative to any of the strains orbacterial species described herein over a specified region or over theentire sequence. It would be appreciated by one of skill in the art thatthe term “homology” or “percent homology,” in the context of two or morenucleic acid sequences or amino acid sequences, refers to a measure ofsimilarity between two or more sequences or portion(s) thereof. Thehomology may exist over a region of a sequence that is at least about 50nucleotides in length, or more preferably over a region that is 100 to500 or 1000 or more nucleotides in length. In some embodiments, thehomology exists over the length the 16S rRNA or 16S rDNA sequence, or aportion thereof.

Additionally, or alternatively, two or more sequences may be assessedfor the identity between the sequences. The terms “identical” or percent“identity” in the context of two or more nucleic acids or amino acidsequences, refer to two or more sequences or subsequences that are thesame. Two sequences are “substantially identical” if two sequences havea specified percentage of amino acid residues or nucleotides that arethe same (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%,99.6%, 99.7%, 99.8% or 99.9% identical) over a specified region or overthe entire sequence, when compared and aligned for maximumcorrespondence over a comparison window, or designated region asmeasured using one of the following sequence comparison algorithms or bymanual alignment and visual inspection. Optionally, the identity existsover a region that is at least about 50 nucleotides in length, or morepreferably over a region that is 100 to 500 or 1000 or more nucleotidesin length. In some embodiments, the identity exists over the length the16S rRNA or 16S rDNA sequence.

Additionally, or alternatively, two or more sequences may be assessedfor the alignment between the sequences. The terms “alignment” orpercent “alignment” in the context of two or more nucleic acids or aminoacid sequences, refer to two or more sequences or subsequences that arethe same. Two sequences are “substantially aligned” if two sequenceshave a specified percentage of amino acid residues or nucleotides thatare the same (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%,99.5%, 99.6%, 99.7%, 99.8% or 99.9% identical) over a specified regionor over the entire sequence, when compared and aligned for maximumcorrespondence over a comparison window, or designated region asmeasured using one of the following sequence comparison algorithms or bymanual alignment and visual inspection. Optionally, the alignment existsover a region that is at least about 50 nucleotides in length, or morepreferably over a region that is 100 to 500 or 1000 or more nucleotidesin length. In some embodiments, the identity exists over the length the16S rRNA or 16S rDNA sequence.

For sequence comparison, typically one sequence acts as a referencesequence, to which test sequences are compared. Methods of alignment ofsequences for comparison are well known in the art. See, e.g., by thelocal homology algorithm of Smith and Waterman (1970) Adv. Appl. Math.2:482c, by the homology alignment algorithm of Needleman and Wunsch, J.Mol. Biol. 48:443, 1970, by the search for similarity method of Pearsonand Lipman. Proc. Natl. Acad. Sci. USA 85:2444, 1988, by computerizedimplementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA inthe Wisconsin Genetics Software Package, Genetics Computer Group.Madison. Wis.), or by manual alignment and visual inspection (see. e.g.,Brent et al., Current Protocols in Molecular Biology, John Wiley & Sons,Inc. (Ringbou ed., 2003)). Two examples of algorithms that are suitablefor determining percent sequence identity and sequence similarity arethe BLAST and BLAST 2.0 algorithms, which are described in Altschul etal., Nuc. Acids Res. 25:3389-3402, 1977; and Altschul et al., J. Mol.Biol. 215:403-410, 1990, respectively.

In one aspect, the disclosure provides compositions comprising multiplepurified bacterial strains. In one aspect, the 16S rDNA sequences ofpurified bacterial strains of the compositions were compared to 16S rDNAsequences of known bacterial species/strains in a bacterial genomedatabase to identify the closest known related bacterial species to thebacterial strains disclosed herein (See e.g., Table 1 and Table 3). Itshould be appreciated that multiple bacterial strains of thecompositions disclosed herein may have the same closest relatedbacterial species. In one aspect, the disclosure provides compositionscomprising one or more bacterial strains or species with 16S rDNAsequences that have homology to a nucleic acid sequence of any one ofthe sequences provided by SEQ ID NOs:1-26. In some embodiments, thespecies with 16S rDNA sequences with homology to a nucleic acid sequenceof any one of the closest related species to any of the strainsdescribed herein, correspond to bacterial strains with 16S rDNAsequences provided by SEQ ID NOs:27-52. In one aspect, the disclosureprovides compositions comprising one or more bacterial strains orspecies with 16S rDNA sequences that have homology to a nucleic acidsequence of any one of the sequences provided by SEQ ID NOs:1-21. Insome embodiments, the species with 16S rDNA sequences with homology to anucleic acid sequence of any one of the closest related species to anyof the strains described herein, correspond to bacterial strains with16S rDNA sequences provided by SEQ ID NOs:27-47. In one aspect, thedisclosure provides compositions comprising one or more bacterialstrains or species with 16S rDNA sequences that have homology to anucleic acid sequence of any one of the sequences provided by SEQ IDNOs:1-11. In some embodiments, the species with 16S rDNA sequences withhomology to a nucleic acid sequence of any one of the closest relatedspecies to any of the strains described herein, correspond to bacterialstrains with 16S rDNA sequences provided by SEQ ID NOs:27-37. In oneaspect, the disclosure provides compositions comprising one or morebacterial strains or species with 16S rDNA sequences that have homologyto a nucleic acid sequence of any one of the sequences provided by SEQID NOs:12-26. In some embodiments, the species with 16S rDNA sequenceswith homology to a nucleic acid sequence of any one of the closestrelated species to any of the strains described herein, correspond tobacterial strains with 16S rDNA sequences provided by SEQ ID NOs:38-52.In one aspect, the disclosure provides compositions comprising one ormore bacterial strains or species with 16S rDNA sequences that havehomology to a nucleic acid sequence of any one of the sequences providedby SEQ ID NOs:12-21. In some embodiments, the species with 16S rDNAsequences with homology to a nucleic acid sequence of any one of theclosest related species to any of the strains described herein,correspond to bacterial strains with 16S rDNA sequences provided by SEQID NOs:38-47.

In some embodiments, the compositions disclosed herein provide at leastone of the bacterial strains (e.g., purified bacterial strains)described herein. In some embodiments, the compositions that comprise atleast one bacterial strain, comprise at least one bacterial strain witha 16S rDNA sequence selected from any one of SEQ ID NOs:1-26. In someembodiments, the compositions that comprise at least one bacterialstrain, comprise at least one bacterial strain with a 97% homology to16S rDNA sequence selected from any one of SEQ ID NOs:1-26. In someembodiments, the compositions that comprise at least one bacterialstrain, comprise at least one bacterial strain with a 97% sequenceidentity with a 16S rDNA sequence selected from any one of SEQ IDNOs:1-26. In some embodiments, the compositions disclosed hereincomprise two or more bacterial strains. In some embodiments, thecompositions described herein comprise at least 2, at least 3, at least4, at least 5, at least 6, at least 7, at least 8, at least 9, at least10, at least 11, at least 12, at least 13, at least 14, at least 15, atleast 16, at least 17, at least 18, at least 19, or at least 20 or morebacterial strains (e.g., purified bacterial strains).

In some embodiments of the compositions provided herein, at least 50% ofthe bacterial strains belong to the order of Bacteriodales. In someembodiments of the compositions provided herein, at least 50% of thebacterial strains belong to the genus Bacteroides or Parabacteroides. Insome embodiments of the compositions provided herein, one or morestrains belongs to the genus Bacteroides and one or more strains belongsto the genus Parabacteroides. In some embodiments of the compositionsprovided herein, at least 25% of the bacterial strains belong to thefamily of Bacteroidaceae. In some embodiments of the compositionsprovided herein, one or more of the bacterial strains belongs to thegenus Bacteroides. In some embodiments of the compositions providedherein, one or more of the bacterial strains belongs to the genusParabacteroides. In some embodiments of the compositions providedherein, the composition does not include bacterial strains that belongto the order of Bacteriodales.

In some embodiments of the compositions provided herein, one or more ofthe bacterial strains belong to the order of Bacteriodales and one ormore of the bacterial strains belong to the order of Clostridiales. Insome embodiments of the compositions provided herein, at least 50% ofthe bacterial strains belong to the order of Bacteriodales and one ormore of the bacterial strains belong to the order of Clostridiales. Insome embodiments of the compositions provided herein, at least 75% ofthe bacterial strains belong to the order of Bacteriodales and one ormore of the bacterial strains belong to the order of Clostridiales. Insome embodiments of the compositions provided herein, at least 90% ofthe bacterial strains belong to the order of Bacteriodales and one ormore of the bacterial strains belong to the order of Clostridiales. Insome embodiments, the compositions provided herein do not include E.coli. In some embodiments, the compositions provided herein do notinclude Bifidobacterium. In some embodiments, the compositions providedherein do not include Bacillus. In some embodiments, the compositionsprovided herein do not include Enterococcus. In some embodiments, thecompositions provided herein do not include Barnesiella. In someembodiments, the compositions provided herein do not include B.fragilis. In some embodiments, the compositions provided herein do notinclude B. thetaiotaomicron. In some embodiments, the compositionsprovided herein do not include Akkermansia. In some embodiments, thecompositions provided herein do not include Proteobacteria. In someembodiments, the compositions provided herein do not includeBurkholderia. In some embodiments, the compositions provided herein donot include clostridium species belonging to Cluster IV. In someembodiments, the compositions provided herein do not includeFaecalibacterium. In some embodiments, the compositions provided hereindo not include clostridium species belonging to Cluster XIVa. In someembodiments, the compositions do not comprise fungi, such as Monillaspecies.

In one aspect, the disclosure provides purified fractions of human stoolsample that can induce CD8 T cells.

In some embodiments of the compositions provided herein, one or more ofthe bacterial strains are human-derived bacteria. In some embodiments ofthe compositions provided herein, all of the bacterial strains arehuman-derived bacteria. In some embodiments of the compositions providedherein, the bacterial strains are derived from more than one humandonor.

The bacterial strains used in the compositions provided herein generallyare isolated from the microbiome of healthy individuals. In someembodiments, the compositions include strains originating from a singleindividual. In some embodiments, the compositions include strainsoriginating from multiple individuals. In some embodiments, thebacterial strains are obtained from multiple individuals, isolated andgrown up individually. The bacterial compositions that are grown upindividually may subsequently be combined to provide the compositions ofthe disclosure. It should be appreciated that the origin of thebacterial strains of the compositions provided herein is not limited tothe human microbiome from a healthy individual. In some embodiments, thebacterial strains originate from a human with a microbiome in dysbiosis.In some embodiments, the bacterial strains originate from non-humananimals or the environment (e.g., soil or surface water). In someembodiments, the combinations of bacterial strains provided hereinoriginate from multiple sources (e.g., human and non-human animals).

In some embodiments of the compositions provided herein, the compositionincludes one or more anaerobic bacteria. In some embodiments of thecompositions provided herein, the composition includes only anaerobicbacteria. In some embodiments of the compositions provided herein, thecomposition includes one or more facultative anaerobic bacteria. In someembodiments of the compositions provided herein, the compositionincludes only facultative anaerobic bacteria. In some embodiments of thecompositions provided herein, the composition includes one or moreobligate anaerobic bacteria. In some embodiments of the compositionsprovided herein, the composition includes only obligate anaerobicbacteria. In some embodiments of the compositions provided herein, oneor more of the bacterial strains does not have an antibiotic resistancegene. In some embodiments of the compositions provided herein, thebacterial strains do not have an antibiotic resistance gene that rendersthe bacterial strain resistant to vancomycin.

In some embodiments of the compositions provided herein, thecompositions do not include bacterial strains that are resistant to oneor more antibiotics. It should be appreciated that it may be desirableto have a mechanism to remove the bacterial compositions provided hereinfrom the body after administration. One such mechanism is to remove thebacterial compositions by antibiotic treatment. Thus, in someembodiments, the compositions do not include bacterial strains that areresistant to one or more antibiotics. In some embodiments, thecompositions do not include bacterial strains that are resistant to oneor more antibiotics selected from the group consisting of penicillin,benzylpenicillin, ampicillin, sulbactam, amoxicillin, clavulanate,tazobactam, piperacillin, cefmetazole, vancomycin, imipenem, meropenem,metronidazole and clindamycin. In some embodiments, the compositions donot include bacterial strains that are resistant to vancomycin.

In some embodiments, the compositions include bacterial strains that aresusceptible to at least four antibiotics that are efficacious in humans.In some embodiments, the compositions include bacterial strains that aresusceptible to at least three antibiotics that are efficacious inhumans. In some embodiments, the compositions include bacterial strainsthat are susceptible to at least two antibiotics that are efficacious inhumans. In some embodiments, the compositions include bacterial strainsthat are susceptible to at least one antibiotic that is efficacious inhumans. In some embodiments, the compositions include only bacterialstrains that are susceptible to at least four antibiotics that areefficacious in humans. In some embodiments, the compositions includeonly bacterial strains that are susceptible to at least threeantibiotics that are efficacious in humans. In some embodiments, thecompositions include only bacterial strains that are susceptible to atleast two antibiotics that are efficacious in humans. In someembodiments, the compositions include bacterial strains that aresusceptible to at least one antibiotic that is efficacious in humans.(An “antibiotic that is efficacious in a human” as used herein is anantibiotic that has been used to successfully treat bacterial infectionsin a human).

In some embodiments of the compositions provided herein, one or more ofthe bacterial strains is a spore-former. In some embodiments of thecompositions provided herein, one or more of the bacterial strains is inspore form. In some embodiments of the compositions provided herein, oneor more of the bacterial strains is a non-spore former. In someembodiments, the compositions described herein comprise spore formingand non-spore forming bacterial strains. In some embodiments, thecompositions described herein comprise spore-forming bacterial strains.In some embodiments, the compositions described herein comprise onlyspore-forming bacterial strains. In some embodiments, the compositionsdescribed herein comprise only non-spore forming bacterial strains. Thespore-forming bacteria can be in spore form (i.e., as spores) or invegetative form (i.e., as vegetative cells). In spore form, bacteria aregenerally more resistant to environmental conditions, such as heat,acid, radiation, oxygen, chemicals, and antibiotics. In contrast, in thevegetative state or actively growing state, bacteria are moresusceptible to such environmental conditions, compared to in the sporeform. In general, bacterial spores are able to germinate from the sporeform into a vegetative/actively growing state, under appropriateconditions. For instance, bacteria in spore format may germinate whenthey are introduced in the intestine.

In some embodiments, at least one (e.g., 1, 2, 3, 4, 5, or more) of thebacterial strains in the composition is a spore former. In someembodiments, at least one (e.g., 1, 2, 3, 4, 5, or more) of thebacterial strains in the composition is in spore form. In someembodiments, at least one (e.g., 1, 2, 3, 4, 5, or more) of thebacterial strains in the composition is a non-spore former. In someembodiments, at least one (e.g., 1, 2, 3, 4, 5, or more) of thebacterial strains in the composition is in vegetative form (as discussedabove, spore forming bacteria can also be in vegetative form). In someembodiments, at least one (e.g., 1, 2, 3, 4, 5, or more) of thebacterial strains in the composition is in spore form and at least one(e.g., 1, 2, 3, 4, 5, or more) of the bacterial strains in thecomposition is in vegetative form. In some embodiments, at least onebacterial strain that is considered able to form spores (i.e., aspore-former) but is present in the composition in vegetative form. Insome embodiments, at least one bacterial strain that is considered ableto form spores is present in the composition both in spore form and invegetative form.

It is envisioned that the bacterial strains of the compositions providedherein are alive and will be alive when they reach the target area(e.g., the intestines). Bacterial spores are considered to be alive inthis regards. In some embodiments, bacteria that are administered asspores may germinate in the target area (e.g., the intestines). Itshould further be appreciated that not all of the bacteria are alive andthe compositions can include a percentage (e.g., by weight) that is notalive. In addition, in some embodiments, the compositions includebacterial strains that are not alive when administered or at the timewhen the composition reaches the target area (e.g., the intestines). Itis envisioned that non-living bacteria may still be useful by providingsome nutrients and metabolites for the other bacterial strains in thecomposition.

In any of the compositions provided herein, in some embodiments, thebacterial strains are purified. In any of the compositions providedherein, in some embodiments, the bacterial strains are isolated. Any ofthe bacterial strains described herein may be isolated and/or purified,for example, from a source such as a culture or a microbiota sample(e.g., fecal matter). The bacterial strains used in the compositionsprovided herein generally are isolated from the microbiome of healthyindividuals. However, bacterial strains can also be isolated fromindividuals that are considered not to be healthy. In some embodiments,the compositions include strains originating from multiple individuals.As used herein, the term “isolated” bacteria that have been separatedfrom one or more undesired component, such as another bacterium orbacterial strain, one or more component of a growth medium, and/or oneor more component of a sample, such as a fecal sample. In someembodiments, the bacteria are substantially isolated from a source suchthat other components of the source are not detected. As also usedherein, the term “purified” refers to a bacterial strain or compositioncomprising such that has been separated from one or more components,such as contaminants. In some embodiments, the bacterial strain issubstantially free of contaminants. In some embodiments, one or morebacterial strains of a composition may be independently purified fromone or more other bacteria produced and/or present in a culture or asample containing the bacterial strain. In some embodiments, a bacterialstrain is isolated or purified from a sample and then cultured under theappropriate conditions for bacterial replication, e.g., under anaerobicculture conditions. The bacteria that is grown under appropriateconditions for bacterial replication can subsequently beisolated/purified from the culture in which it is grown.

In one aspect, the disclosure provides bacterial strains and mixtures ofbacterial strains with unique biological properties. In some embodimentsof the compositions provided herein, the composition inducesproliferation and/or accumulation of CD8+ T-cells. In some embodiments,the bacterial strains of the compositions provided herein can induceproliferation and/or accumulation of CD8+ T-cells, because of thesynergy between the bacterial strains. Thus, without being limiting to aspecific mechanism, in some embodiments, the combination of thebacterial strains of the compositions provided herein actsynergistically in the induction of proliferation and/or accumulation ofCD8+ T-cells because the combination of the strains is particularlywell-suited to generate metabolites and/or cellular signals thatstimulate the induction of proliferation and/or accumulation of CD8+T-cells. The bacterial compositions may do so, for instance through theuse of nutrients in the intestinal tract (e.g., the colon or the cecum),and/or metabolic interactions that result in metabolites and/or cellularsignals that stimulate the induction of proliferation and/oraccumulation of CD8+ T-cells. In addition, without being limiting to aspecific mechanism, in some embodiments, the combination of thebacterial strains of the compositions provided herein actsynergistically in the induction of proliferation and/or accumulation ofCD8+ T-cells because the combination of the strains is superior inengrafting specific niches in the intestinal tract (e.g., the colon orthe cecum) that will result in the induction of proliferation and/oraccumulation of CD8+ T-cells (e.g., by providing a favorablemicroenvironment). In some embodiments, the combination of the bacterialstrains of the compositions provided herein act synergistically in theinduction of proliferation and/or accumulation of CD8+ T-cells becausethe combination of the strains is particularly well-suited to generatemetabolites and/or cellular signals that stimulate the induction ofproliferation and/or accumulation of CD8+ T-cells, and the combinationis well suited to engraft in specific niches, that result inlocalization of the metabolites and/or cellular signals to a target forthe induction of proliferation and/or accumulation of CD8+ T-cells

Treatment of Diseases

Cancer

In one aspect, the disclosure includes compositions and methods for thetreatment of diseases in a subject. In some embodiments of the methodsprovided herein, the subject has cancer. In one aspect, the cancers thatcan be treated according to the compositions and methods providedherein, include without limitation, carcinoma, glioma, mesothelioma,melanoma, lymphoma, leukemia, adenocarcinoma, breast cancer, ovariancancer, cervical cancer, glioblastoma, multiple myeloma, prostatecancer, Burkitt's lymphoma, head and neck cancer, colon cancer,colorectal cancer, non-small cell lung cancer, small cell lung cancer,cancer of the esophagus, stomach cancer, pancreatic cancer,hepatobiliary cancer, cancer of the gallbladder, cancer of the smallintestine, rectal cancer, kidney cancer, bladder cancer, prostatecancer, penile cancer, urethral cancer, testicular cancer, vaginalcancer, uterine cancer, thyroid cancer, parathyroid cancer, adrenalcancer, pancreatic endocrine cancer, carcinoid cancer, bone cancer, skincancer, retinoblastomas, Hodgkin's lymphoma, non-Hodgkin's lymphoma,Kaposi's sarcoma, multicentric Castleman's disease, AIDS-associatedprimary effusion lymphoma, neuroectodermal tumors, or rhabdomyosarcoma.In some embodiments of the methods provided herein, the cancer isprostate cancer, bladder cancer, non-small cell lung cancer, urothelialcarcinoma, melanoma, or renal cell carcinoma. In some embodiments of themethods provided herein, the subject is undergoing radiation treatment.

In some embodiments of the methods provided herein, the method furtherincludes administering one or more anticancer agents. In someembodiments of the methods provided herein, the anticancer agent is achemotherapy agent. In some embodiments of the methods provided herein,the anticancer agent is a cancer immunotherapy agent. In someembodiments of the methods provided herein, the cancer immunotherapyagent is an immune checkpoint inhibitor. In some embodiments of themethods provided herein, the immune checkpoint inhibitor is a PD-1inhibitor, PD-L-1 inhibitor, or CTLA-4 inhibitor. In some embodiments ofthe methods provided herein, the immune checkpoint inhibitor is a PD-1inhibitor. In some embodiments of the methods provided herein, theimmune checkpoint inhibitor is a CTLA-4 inhibitor.

In some embodiments of the methods provided herein, the cancerimmunotherapy agent is a cancer vaccine that acts to increase theresponse of a subject's immune system to cancer cells. For example,cancer vaccines include cancer antigen(s) that act to induce orstimulate an immune response against cells bearing the cancerantigen(s). The immune response induced or stimulated can include anantibody (humoral) immune response and/or a T-cell (cell-mediated)immune response. CD8+ T-cells can differentiate into cytotoxic T-cellsthat kill target cells bearing the antigen recognized by CD8+ T-cells.Induction of CD8+ T-cells can, therefore, enhance the immune response tocancer antigens provided in a cancer vaccine. In some embodiments of themethods provided herein, the cancer immunotherapy agent is a CAR-Ttherapeutic. CAR-T cells include T-cells taken from a patient that aregenetically engineered to produce chimeric antigen receptors (CARs) ontheir surface. The CARs are engineered to recognize a specific antigenon cancer cells. After the CAR-T cells are infused into the patient,they recognize and kill cancer cells that express the specific antigenon their surfaces. Induction of CD8+ T-cells is useful to provide cellsfor conversion into CAR-T cells.

In some embodiments of the methods provided herein, the method furtherincludes administering one or more cytokines. In some embodiments of themethods provided herein the cytokine is IL-2, IL-15, or IL-21. In someembodiments of the methods provided herein, the method further includesadministering one or more costimulatory agents. In some embodiments ofthe methods provided herein the costimulatory agent is a CD-28, OX-40,4-1BB, or CD40 antibody. In some embodiments of the methods providedherein, the method further includes administering one or more vaccines.In some embodiments of the methods provided herein, the vaccine is adendritic cell vaccine. In some embodiments of the methods providedherein, the method further includes administering adoptive cell transfertherapy. In some embodiments of the methods provided herein, theadoptive cell transfer therapy is the use of engineered T-cell receptorsor chimeric antigen receptors.

In some embodiments of the compositions provided herein, the compositionfurther comprises one or more anticancer agents. In some embodiments ofthe compositions provided herein, the anticancer agent is a chemotherapyagent. In some embodiments of the compositions provided herein, theanticancer agent is cancer immunotherapy agent. In some embodiments ofthe compositions provided herein, the cancer immunotherapy agent is animmune checkpoint inhibitor. In some embodiments of the compositionsprovided herein, the immune checkpoint inhibitor is a PD-1 inhibitor,PD-L-1 inhibitor, or CTLA-4 inhibitor. In some embodiments of thecompositions provided herein, the immune checkpoint inhibitor is a PD-1inhibitor, PD-L-1 inhibitor, CTLA-4 inhibitor, IDO1 inhibitor, LAG3inhibitor or TIM3 inhibitor. In some embodiments of the compositionsprovided herein, the immune checkpoint inhibitor is a PD-1 inhibitor. Insome embodiments, the PD-1 inhibitor is nivolumab. In some embodiments,the PD-1 inhibitor is pembrolizumab. In some embodiments, the PD-1inhibitor is pidiluzimab. In some embodiments of the compositionsprovided herein, the immune checkpoint inhibitor is a PD-L-1 inhibitor.In some embodiments, the PD-L-1 inhibitor is atezolizumab. In someembodiments, the PD-L-1 inhibitor is avelumab. In some embodiments, thePD-L-1 inhibitor is durvalumab. In some embodiments of the methodsprovided herein, the immune checkpoint inhibitor is a CTLA-4 inhibitor.In some embodiments, the CTLA-4 inhibitor is an anti-CTLA-4 antibody.Examples of anti-CTLA-4 antibodies include, without limitation,ipilimumab, tremelimumab (CP-675,206), 9H10, 4F10, and 9D9. In someembodiments, the CTLA-4 inhibitor is ipilimumab. In some embodiments,the CTLA-4 inhibitor is tremelimumab. It should further be appreciatedthat multiple anticancer agents (e.g., immune checkpoint inhibitors) maybe included in the compositions and methods disclosed herein. Forinstance, in a non-limiting example, the compositions and methodsdisclosed include both a PD-1 inhibitor and a CTLA-4 inhibitor.

In one aspect, the disclosure provides a composition comprising apurified bacterial mixture comprising Phascolarctobacterium faecium,Fusobacterium ulcerans, Bacteroides dorei, Bacteroides uniformis,Subdoligranulum sp., Paraprevotella xylaniphila, Parabacteroidesjohnsonii, Alistipes sp., Parabacteroides gordonii, Eubacterum limosum,and Parabacteroides distasonis, and a PD-1 inhibitor. In one aspect, thedisclosure provides a composition comprising a purified bacterialmixture comprising Phascolarctobacterium faecium, Fusobacteriumulcerans, Bacteroides dorei, Bacteroides uniformis, Subdoligranulum sp.,Paraprevotella xylaniphila, Parabacteroides johnsonii, Alistipes sp.,Parabacteroides gordonii, Eubacterum limosum, and Parabacteroidesdistasonis, and a PD-L-1 inhibitor. In one aspect, the disclosureprovides a composition comprising a purified bacterial mixturecomprising Phascolarctobacterium faecium, Fusobacterium ulcerans,Bacteroides dorei, Bacteroides uniformis, Subdoligranulum sp.,Paraprevotella xylaniphila, Parabacteroides johnsonii, Alistipes sp.,Parabacteroides gordonii, Eubacterum limosum, and Parabacteroidesdistasonis, and a CTLA-4 inhibitor.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising bacterial strains comprising 16SrDNA sequences of at least 97% homology to SEQ ID NO:1, SEQ ID NO:2, SEQID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ IDNO:8, SEQ ID NO:9, SEQ ID NO:10, and SEQ ID NO:11, and a PD-1 inhibitor.In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising bacterial strains comprising 16SrDNA sequences of at least 97% homology to SEQ ID NO:1, SEQ ID NO:2, SEQID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ IDNO:8, SEQ ID NO:9, SEQ ID NO:10, and SEQ ID NO:11, and a PD-L-1inhibitor. In one aspect, the disclosure provides compositionscomprising a purified bacterial mixture comprising bacterial strainscomprising 16S rDNA sequences of at least 97% homology to SEQ ID NO:1,SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ IDNO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, and SEQ ID NO:11, and aCTLA-4 inhibitor.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising bacterial strains comprising 16SrDNA sequences of at least 97% sequence identity with SEQ ID NO:1, SEQID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ IDNO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, and SEQ ID NO:11, and aPD-1 inhibitor. In one aspect, the disclosure provides compositionscomprising a purified bacterial mixture comprising bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ IDNO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, and SEQ IDNO:11, and a PD-L-1 inhibitor. In one aspect, the disclosure providescompositions comprising a purified bacterial mixture comprisingbacterial strains comprising 16S rDNA sequences of at least 97% sequenceidentity with SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ IDNO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10,and SEQ ID NO:11, and a CTLA-4 inhibitor.

In one aspect, the disclosure provides compositions comprising apurified bacterial mixture comprising bacterial strains comprising 16SrDNA sequences of at least 97% sequence identity with SEQ ID NO:54, SEQID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ IDNO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, and SEQ ID NO:64, and aPD-1 inhibitor. In one aspect, the disclosure provides compositionscomprising a purified bacterial mixture comprising bacterial strainscomprising 16S rDNA sequences of at least 97% sequence identity with SEQID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ IDNO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, and SEQID NO:64, and a PD-L-1 inhibitor. In one aspect, the disclosure providescompositions comprising a purified bacterial mixture comprisingbacterial strains comprising 16S rDNA sequences of at least 97% sequenceidentity with SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57,SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62,SEQ ID NO:63, and SEQ ID NO:64, and a CTLA-4 inhibitor.

In some embodiments of the compositions provided herein, the compositionfurther includes one or more cytokines. In some embodiments of thecompositions provided herein, the cytokine is IL-2, IL-15, or IL-21. Insome embodiments of the compositions provided herein, the compositionfurther comprises one or more costimulatory agents. In some embodimentsof the compositions provided herein, the costimulatory agent is a CD-28,OX-40, 4-1BB, or CD40 antibody. In some embodiments of the compositionsprovided herein, the composition further comprises one or more vaccines.In some embodiments of the compositions provided herein, the vaccine isa dendritic cell vaccine. In some embodiments of the compositionsprovided herein, the composition is combined with adoptive cell transfertherapy. In some embodiments of the compositions provided herein, theadoptive cell transfer therapy is the use of engineered T-cell receptorsor chimeric antigen receptors.

Infectious Disease

In one aspect, the disclosure includes compositions and methods for thetreatment of diseases in a subject. In some embodiments of the methodsprovided herein, the subject has an infectious disease. In someembodiments of the methods provided herein, the infectious disease is abacterial infection, a viral infection, a parasitic infection, or afungal infection. In some embodiments of the methods provided herein,the infectious disease is a viral infection. In some embodiments of themethods provided herein, the viral infection is HIV. In some embodimentsof the methods provided herein, the infection is an infection by ahepatitis virus. In some embodiments, the compositions provided hereincan be used as a pharmaceutical composition for preventing or treating(reducing, partially or completely the adverse effects of) an infectiousdisease, such as a bacterial infection, a viral infection, a parasiticinfection, and a fungal infection.

Bacterial infections that can be treated according to the methodsprovided herein include, but are not limited to P. aeruginosa, E. coli,C. tetani, N. gonorrhoeae, C. botulinum, Klebsiella sp., Serratia sp.,Pseudomanas sp., P. cepacia, Acinetobacter sp., S. epidermis, E.faecalis, S. pneumonias, S. aureus, S. mutans, Haemophilus sp.,Neisseria Sp., N. meningitides, Bacteroides sp., Citrobacter sp.,Branhamella sp., Salmonella sp., Shigella sp., S. pyogenes, Proteus sp.,Clostridium sp., Erysipelothrix sp., Listeria sp., Pasteurellamultocida, Streptobacillus sp., Spirillum sp., Fusospirocheta sp.,Treponema pallidum, Borrelia sp., Actinomycetes, Mycoplasma sp.,Chlamydia sp., Rickettsia sp., Spirochaeta, Borellia burgdorferi,Legionella sp., Mycobacteria sp, Ureaplasma sp, Streptomyces sp.,Trichomoras sp., P. mirabilis; Vibrio cholera, enterotoxigenicEscherichia coli, Clostridium difficile, Salmonella typhi, C.diphtheria, Mycobacterium leprae, Mycobacterium lepromatosi. Bacterialinfections caused by drug resistant bacteria that can be treatedaccording to the methods provided herein include, but are not limited toClostridium perfringens; Clostridium botulinum; Clostridium tributrycum;Clostridium sporogenes; Escherichia coli; Pseudomonas aeruginosa, suchas Multidrug Resistant Pseudomonas aeruginosa; Vancomycin ResistantEnterococci (VRE); Carbapenem Resistant Enterobacteriaceae (CRE);Neisseria gonorrheae; Acinetobacter, Multidrug Resistant Acinetobacter;Campylobacter; Multidrug-resistant Campylobacter; Candida,Fluconazole-Resistant Candida, Extended spectrum beta-lactamase (ESBL)producing Enterobacteriaceae; Salmonella, Salmonella Typhimurium, Drugresistant non-typhoid Salmonella spp.; Drug resistant Salmonella Typhi;Drug resistant Shigella; Staphylococcus aureus, such as MethicillinResistant S. aureus or vancomycin resistant S. aureus; Drug resistantStreptococcus pneumoniae; Drug resistant Tuberculosis; ErythromycinResistant Group A Streptococcus; Clindamycin resistant Group BStreptococcus, and any combinations thereof.

Viral infections that can be treated according to the methods providedherein include, but are not limited to, picornaviridae, caliciviridae,togaviridae, flaviviridae, coronaviridae, rhabdoviridae, filoviridae,paramyxoviridae, orthomyxoviridae, bunyaviridae, arenaviridae,reoviridae, retroviridae, hepadnaviridae, parvoviridae, papovaviridae,adenoviridae, herpesviridae, poxviridae, rotavirus, parainfluenza virus,influenza virus A and B, hepatitis virus, syphilis, HIV, rabies virus,Epstein-Barr virus, and herpes simplex virus.

Viral infections that can be treated according to the methods providedherein include, but are not limited to Plasmodium falciparum, P. vivax,P. ovale, P. malaria, Toxoplasma gondii, Leishmania mexicana, L.tropica, L. major, L. aethiopica, L. donovani, Trypanosoma cruzi, T.brucei, Schistosoma mansoni, S. haematobium, S. japonium, Trichinellaspiralis, Wuchereria bancrofti, Brugia malayli, Entamoeba histolytica,Enterobius vermiculoarus, Taenia solium, T. saginata, Trichomonasvaginatis, T. hominis, T. tenax; Giardia lamblia, Cryptosporidiumparvum, Pneumocytis carinii, Babesia bovis, B. divergens, B. microti,Isospore belli, L. hominis, Dientamoeba jragiles, Onchocerca volvulus,Ascaris lumbricoides, Necator americanis, Ancylostoma duodenale,Strongyloides stercoralis, Capillaria philippinensis, Angiostrongyluscantonensis, Hymenolepis nana, Diphyllobothrium latum, Echinococcusgranulosus, E. multilocularis, Paragonimus westermani, P. caliensis,Chlonorchis sinensis, Opisthorchis felineas, G. Viverini, Fasciolahepatica, Sarcoptes scabiei, Pediculus humanus, Phthirius pubis, andDermatobia hominis.

Fungal infections that can be treated according to the methods providedherein include, but are not limited to Cryptococcus neoformans,Blastomyces dermatitidis, Aiellomyces dermatitidis, Histoplasfriacapsulatum, Coccidioides immitis, Candida species, including C.albicans, C. tropicalis, C. parapsilosis, C. guilliermondii and C.krusei, Aspergillus species, including A. fumigatus, Aflavus, A. niger,Rhizopus species, Rhizomucor species, Cunninghammella species,Apophysomyces species, including A. saksenaea, A. mucor and A. absidia,Sporothrix schenckii, Paracoccidioides brasiliensis, Pseudallescheriaboydii, Torulopsis glabrata; and Dermatophyres species.

In one aspect, the disclosure provides a vaccine comprising any of thecompositions provided herein and an antigen. In some embodiments of thevaccines provided herein, the antigen is an HIV antigen. In someembodiments of the vaccines provided herein, the antigen

is a hepatitis antigen. In some embodiments, the bacterial compositionsare administered as an adjuvant in combination with antigenic material.The antigenic material can include one or more portions of the proteincoat, protein core, or functional proteins and peptides of a pathogen,or a full pathogen (live, killed, inactivated, or attenuated), or maycomprise one or a plurality of cancer epitopes or cancer antigens. Theantigenic material can be co-administered, administered before, or afterthe bacterial composition. The bacterial composition may also beadministered with existing mucosal vaccines such as influenza vaccines,(e.g. FluMist from Medimmune or NASOVAC from Serum Institute of India),rotavirus vaccines (e.g. RotaTeq from Merck or Rotarix fromGlaxoSmithKline), typhoid vaccines (e.g. Vivotif from Crucell, Ty21A),cholera vaccines (e.g. Orochol from Crucell, Shanchol from ShanthaBiotechnics), traveller's diarrhea vaccines (e.g. Dukoral from Crucell),and with antigens of live attenuated Influenza A virus HI strain, liveattenuated Influenza A virus H3 strain, Influenza B virus, liveattenuated H1N1 influenza virus (swine flu), live attenuated rotavirus,mono- and multi-valent poliovirus, live attenuated Salmonella Typhi,live recombinant Vibrio cholerae lacking cholera toxin subunit A, wholekilled Vibrio cholerae 01 classical and El Tor biotypes with or withoutcholera toxin subunit B, cancer antigens, cancer epitopes, andcombinations thereof.Autoimmune Disease or Allergic Disease

In one aspect, the disclosure includes compositions and methods for thetreatment of diseases in a subject. In some embodiments of the methodsprovided herein, the subject has an autoimmune disease or an allergicdisease. The compositions and methods of the current disclosure can beused for preventing or treating autoimmune disease and allergic disease.Autoimmune disease that can be treated include, but are not limited to,inflammatory bowel disease, systemic lupus erythematosus, rheumatoidarthritis, multiple sclerosis, or Hashimoto's disease. Allergic diseasesthat can be treated include, but are not limited to, food allergy,pollenosis, or asthma.

Additional examples of autoimmune and allergic disease that can betreated according to the methods and compositions provided hereininclude, without limitation, rejection in organ transplantations, suchas inflammatory bowel disease (IBD), ulcerative colitis, Crohn'sdisease, sprue, autoimmune arthritis, rheumatoid arthritis, Type Idiabetes, multiple sclerosis, graft vs. host disease following bonemarrow transplantation, osteoarthritis, juvenile chronic arthritis, Lymearthritis, psoriatic arthritis, reactive arthritis, spondyloarthropathy, systemic lupus erythematosus, insulin dependent diabetesmellitus, thyroiditis, asthma, psoriasis, dermatitis scleroderma, atopicdermatitis, graft versus host disease, acute or chronic immune diseaseassociated with organ transplantation, sarcoidosis, atherosclerosis,disseminated intravascular coagulation, Kawasaki's disease, Grave'sdisease, nephrotic syndrome, chronic fatigue syndrome, Wegener'sgranulomatosis, Henoch-Schoenlejn purpurea, microscopic vasculitis ofthe kidneys, chronic active hepatitis, uveitis, septic shock, toxicshock syndrome, sepsis syndrome, cachexia, acquired immunodeficiencysyndrome, acute transverse myelitis, Huntington's chorea, Parkinson'sdisease, Alzheimer's disease, stroke, primary biliary cirrhosis,hemolytic anemia, polyglandular deficiency type I syndrome andpolyglandular deficiency type II syndrome, Schmidt's syndrome, adult(acute) respiratory distress syndrome, alopecia, alopecia areata,seronegative arthopathy, arthropathy, Reiter's disease, psoriaticarthropathy, chlamydia, yersinia and salmonella associated arthropathy,spondyloarhopathy, atheromatous disease/arteriosclerosis, allergiccolitis, atopic allergy, food allergies such as peanut allergy, tree nutallergy, egg allergy, milk allergy, soy allergy, wheat allergy, seafoodallergy, shellfish allergy, or sesame seed allergy, autoimmune bullousdisease, pemphigus vulgaris, pemphigus foliaceus, pemphigoid, linear IgAdisease, autoimmune haemolytic anaemia, Coombs positive haemolyticanaemia, acquired pernicious anaemia, juvenile pernicious anaemia,myalgic encephalitis/Royal Free Disease, chronic mucocutaneouscandidiasis, giant cell arteritis, primary sclerosing hepatitis,cryptogenic autoimmune hepatitis, Acquired Immunodeficiency DiseaseSyndrome, Acquired Immunodeficiency Related Diseases, Hepatitis C,common varied immunodeficiency (common variable hypogammaglobulinaemia),dilated cardiomyopathy, fibrotic lung disease, cryptogenic fibrosingalveolitis, postinflammatory interstitial lung disease, interstitialpneumonitis, connective tissue disease associated interstitial lungdisease, mixed connective tissue disease associated lung disease,systemic sclerosis associated interstitial lung disease, rheumatoidarthritis associated interstitial lung disease, systemic lupuserythematosus associated lung disease, dermatomyositis/polymyositisassociated lung disease, Sjogren's disease associated lung disease,ankylosing spondylitis associated lung disease, vasculitic diffuse lungdisease, haemosiderosis associated lung disease, drug-inducedinterstitial lung disease, radiation fibrosis, bronchiolitis obliterans,chronic eosinophilic pneumonia, lymphocytic infiltrative lung disease,postinfectious interstitial lung disease, gouty arthritis, autoimmunehepatitis, type-1 autoimmune hepatitis (classical autoimmune or lupoidhepatitis), type-2 autoimmune hepatitis (anti-LKM antibody hepatitis),autoimmune mediated hypoglycemia, type B insulin resistance withacanthosis nigricans, hypoparathyroidism, acute immune diseaseassociated with organ transplantation, chronic immune disease associatedwith organ transplantation, osteoarthrosis, primary sclerosingcholangitis, idiopathic leucopenia, autoimmune neutropenia, renaldisease NOS, glomerulonephritides, microscopic vasulitis of the kidneys,discoid lupus, erythematosus, male infertility idiopathic or NOS, spermautoimmunity, multiple sclerosis (all subtypes), insulin dependentdiabetes mellitus, sympathetic ophthalmia, pulmonary hypertensionsecondary to connective tissue disease, Goodpasture's syndrome,pulmonary manifestation of polyarteritis nodosa, acute rheumatoid fever,rheumatoid spondylitis, Still's disease, systemic sclerosis, Takayasu'sdisease/arteritis, autoimmune thrombocytopenia, idiopathicthrombocytopenia, autoimmune thyroid disease, hyperthyroidism, goitrousautoimmune hypothyroidism (Hashimoto's disease), atrophic autoimmunehypothyroidism, primary myxoedema, phacogenic uveitis, primaryvasculitis, vitiligo, allergic rhinitis (pollen allergies), anaphylaxis,pet allergies, latex allergies, drug allergies, allergicrhinoconjuctivitis, eosinophilic esophagitis, hypereosinophilicsyndrome, eosinophilic gastroenteritis cutaneous lupus erythematosus,eosinophilic esophagitis, hypereosinophilic syndrome, eosinophilicgastroenteritis, and diarrhea.

In some embodiments of the methods and compositions provided herein, thecomposition further comprises one or more anti-inflammatory agents. Insome embodiments of the methods and compositions provided herein, theanti-inflammatory agent is a non-steroidal anti-inflammatory drug(NSAID). Exemplary NSAIDs include, but are not limited to, aspirin,ibuprofen, naproxen, celecoxib, rofecoxib, diclofenac, diflunisal,etodolac, fenoprofen, flurbiprofen, ketoprofen, ketorolac, mefenamicacid, meloxicam, nabumetone, oxaprozin, piroxicam, sulindac, tolmetinand combinations thereof. In some embodiments, the NSAID is an immuneselective anti-inflammatory derivative (ImSAID).

Treatment of Disease

In one aspect, the disclosure provides compositions and methods oftreatment for disease in a subject. In one aspect, and without beinglimiting, the compositions disclosed herein can treat disease becausetheir administration results in the induction of proliferation and/oraccumulation of CD8+ T-cells. In some embodiments, the disclosureprovides compositions and methods of treatment for disease in a subjectfor diseases that can be treated by the induction of proliferationand/or accumulation of CD8+ T-cells. In some embodiments, the diseasesthat can be treated by the induction of proliferation and/oraccumulation of CD8+ T-cell is cancer, an infectious disease, anautoimmune disease or allergic disease.

In one aspect, the disclosure provides a method of treating a disease ina subject comprising administering any of the compositions providedherein to the subject in an effective amount to treat the disease. Insome embodiments of the methods provided herein, the administration ofthe composition to the subject results in the induction of proliferationand/or accumulation of CD8+ T-cells in the intestine of the subject. Insome embodiments of the methods provided herein, the proliferationand/or accumulation of CD8+ T-cells in the intestine of the subject isincreased by at least 10%, at least 20%, at least 30%, at least 40%, atleast 50%, at least 100%, or at least 200% when compared to theproliferation and/or accumulation of CD8+ T-cells in the intestine ofthe subject before the administration of the composition In someembodiments of the methods provided herein, the administration of thecomposition to the subject results in an increase of IFNγ production inthe intestine of the subject when compared to the IFNγ production in theintestine of the subject before the administration of the composition.In some embodiments of the methods provided herein, the administrationof the composition to the subject results in an increase of IFNγproduction in the intestine of the subject by at least 10%, at least20%, at least 30%, at least 40%, at least 50%, at least 100%, or atleast 200% when compared to the IFN production in the intestine of thesubject before the administration of the composition.

Any of the compositions described herein may be administered to asubject in a therapeutically effective amount or a dose of atherapeutically effective amount to treat or prevent a disease (e.g.,cancer or infectious disease). The terms “treat” or “treatment” refer toreducing or alleviating one or more of the symptoms associated with adisease (e.g., cancer or infectious disease). The terms “prevent” or“prevention” encompass prophylactic administration and may reduce theincidence or likelihood of the occurrence of the disease (e.g., canceror infectious disease). For instance, in some embodiments,administration of the compositions provided herein result in a healthymicrobiome that induces proliferation and/or accumulation of CD8+T-cells thereby protecting a subject against cancer and/or infectiousdisease.

As used herein, a “therapeutically effective amount” of composition,such as a pharmaceutical composition, is any amount that results in adesired response or outcome in a subject, such as those describedherein, including but not limited to prevention of infection, an immuneresponse or an enhanced immune response and/or augmentation of cancertreatment. It should be appreciated that the term effective amount maybe expressed in number of bacteria or CFUs to be administered. It shouldfurther be appreciated that the bacteria can multiply once administered.Thus, administration of even a relatively small amount of bacteria mayhave therapeutic effects.

In some embodiments, the therapeutically effective amount of any of thecompositions described herein is an amount sufficient to treat thedisease, e.g., enhance survival of the subject, suppress an infectionand/or treat the cancer.

Any of the methods described herein may be for the treatment of cancerin a subject. As used herein, methods of treating cancer involverelieving or alleviating at least one symptom associated with thecancer, or slowing or reversing the cancer progression. A method oftreating cancer may, for example, eliminate or reduce a subject's tumorburden, reduce the number or replication of cancer cells, and/orprevent, delay or inhibit metastasis.

Also provided herein are methods for the treatment or prevention of aninfectious disease in a subject. As used herein, methods of treating aninfectious disease may involve relieving or alleviating at least onesymptom associated with infection, or slowing or reversing theprogression of the infection. A method of treating an infectious diseasemay, for example, eliminate or reduce the load of an infectious organism(e.g., bacteria, virus, fungus, or parasite), or inhibit or reduce oneor more symptoms of the infection. As also used herein, the terms“prevent,” “prevention,” and “preventing,” include the administration ofa composition to a subject to reduce, or delay the onset of themanifestation of clinical or subclinical symptoms, complications,pathologies or biochemical indicia of the infection, or to reduce orinhibit the spread/transmission of the infectious organism (e.g.,bacteria, virus, fungus, or parasite).

Aspects of the present disclosure are related to methods for treating adisease or condition in a subject by administering a therapeuticallyeffective amount of any of the compositions described herein. In someembodiments, the subject is a mammalian subject, such as a human,non-human primate, rodent, rabbit, sheep, pig, dog, cat, horse, or cow.In some embodiments, the subject is a human subject. The compositionsand methods described herein may be utilized in conjunction with othertypes of therapy (i.e., combination treatment), such as additionaltherapeutic agents. Examples of additional combination therapiesinclude, without limitation, surgery, radiation, gene therapy, andadministration of additional therapeutic agents, such aschemotherapeutics, antibiotics, antivirals, anti-fungals,anti-parasitics, immunomodulatory agents, anti-inflammatory agents. Ingeneral, combination therapies can be administered simultaneously orsequentially (in any order) with the compositions and methods describedherein. In some embodiments, any of the compositions described herein isadministered simultaneously with one or more additional therapeuticagents, for example in a single dose or in multiple doses that areadministered at substantially the same time.

In some embodiments, the compositions described herein are administeredto a subject concomitantly with one or more additional therapeuticagents. In some embodiments, the compositions described herein areadministered to a subject followed by administration of one or moreadditional therapeutic agent. In some embodiments, any of thecompositions described herein is administered at least about 1 day, 2days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks,5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12weeks, 3 months, 4 months, 5 months, 6 months or more prior toadministration of the one or more additional therapeutic agent.Alternatively, in some embodiments, one or more therapeutic agentadministered to a subject followed by administration of any of thecompositions described herein. In some embodiments, one or moretherapeutic agent is administered at least about 1 day, 2 days, 3 days,4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 3months, 4 months, 5 months, 6 months or more prior to administration ofany the compositions described herein.

Additional Methods

Also within the scope of the present disclosure are methods of assessingwhether one or more bacterial strains of any of the compositionsdescribed herein are present in the intestine of a subject. In someembodiments, if fewer than a threshold number of bacterial strains aredetected in the intestine of the subject, any of the compositionsdescribed herein are administered to the subject to increase the numberof the bacterial strains in the intestine of the subject. In someembodiments, the method further comprises identifying the subject as acandidate for a treatment of the disease based on the number ofbacterial strains detected in the intestine. Measuring the levels of thebiomarker sets may also be useful in the evaluation and treatment of adisease. In general, the bacterial population of the intestine (e.g.,presence or absence of one or more bacterial strains) may be determinedby assessing a sample obtained from the subject, such as a fecal sample.

In some embodiments of the compositions provided herein, administrationof the composition to a subject results in the induction ofproliferation and/or accumulation of CD8+ T-cells in the intestine ofthe subject. In some embodiments of the compositions provided herein,administration of the composition to a subject results in an increase inIFNγ production in the intestine of a subject. In some embodiments ofthe compositions provided herein, administration of the composition to asubject results in the presence of one or more bacterial strains of theadministered composition in the intestine of the subject. In someembodiments of the compositions provided herein, the one or morebacterial strains of the administered composition was not previouslypresent in the intestine of the subject. In some embodiments of thecompositions provided herein, administration of the composition to asubject results in the engraftment of one or more bacterial strains ofthe administered composition in the intestine of the subject. In someembodiments of the compositions provided herein, the one or morebacterial strains of the administered composition was not previouslyengrafted in the intestine of the subject. In some embodiments of thecompositions provided herein, administration of the composition to asubject results in an increase in the number of the bacterial strains ofthe administered composition in the intestine of the subject. In someembodiments of the compositions provided herein, administration of thecomposition to a subject results in an increase in the engrafted numberof the bacterial strains of the administered composition in theintestine of the subject. In some embodiments of the compositionsprovided herein, administration of the composition to a subject resultsin an increase in the abundance of total bacteria of the bacterialstrains of the administered composition in the intestine of the subject.In some embodiments of the compositions provided herein, administrationof the composition to a subject results in an increase in the engraftedtotal bacterial strains of the administered composition in the intestineof the subject.

In one aspect, the disclosure provides a method that includesdetermining if one or more bacterial species of any of the compositionsprovided herein are present in the intestine of a subject, wherein ifless than 100%, less than 90%, less than 80%, less than 70%, less than60%, less than 50%, less than 40%, less than 30%, less than 20%, lessthan 10%, or none of the bacterial species are present, the compositionis administered to the subject. In some embodiments of the methodsprovided herein, the subject is undergoing, or will be undergoing,cancer treatment. In one aspect, the disclosure provides a method fordetermining if a subject is expected to respond positively to cancertreatment, wherein the method includes determining if one or morebacterial species of any of the compositions provided herein are presentin the intestine of a subject, wherein if less than 100%, less than 90%,less than 80%, less than 70%, less than 60%, less than 50%, less than40%, less than 30%, less than 20%, less than 10%, or none of thebacterial species are present, the subject is not expected to respondpositively to cancer treatment. In some embodiments of the methodsprovided herein, the cancer treatment is cancer immunotherapy treatment.

In one aspect, the disclosure provides a method for reducing the risk ofa viral infection in a subject, wherein the method includes determiningif one or more bacterial species of any of the compositions providedherein are present in the intestine of a subject, wherein if less than100%, less than 90%, less than 80%, less than 70%, less than 60%, lessthan 50%, less than 40%, less than 30%, less than 20%, less than 10%, ornone of the bacterial species are present, the composition isadministered to the subject, thereby reducing the risk of a viralinfection in the subject. In some embodiments of the methods providedherein, determining the presence of one or more of the bacterial speciesis done by sequencing fecal matter of the subject.

Pharmaceutical Compositions

In one aspect, the disclosure provides pharmaceutical compositionscomprising the bacterial strains and combinations of bacterial strainsprovided herein. In some embodiments of the compositions providedherein, the composition is a pharmaceutical composition. In someembodiments of the pharmaceutical compositions provided herein, thepharmaceutical composition comprises a pharmaceutically acceptableexcipient. In some embodiments of the pharmaceutical compositionsprovided herein, the pharmaceutical composition is formulated for oraladministration. In some embodiments of the pharmaceutical compositionsprovided herein, the pharmaceutical composition is formulated for rectaladministration. In some embodiments of the pharmaceutical compositionsprovided herein, the pharmaceutical composition is formulated fordelivery to the intestine. In some embodiments of the pharmaceuticalcompositions provided herein, the pharmaceutical composition isformulated for delivery to the colon. In some embodiments of thepharmaceutical compositions provided herein, one or more of thebacterial strains is lyophilized. In some embodiments of thepharmaceutical compositions provided herein, the pharmaceuticalcomposition is in the form of a capsule. In some embodiments of thepharmaceutical compositions provided herein, the pharmaceuticalcomposition further comprises a pH sensitive composition comprising oneor more enteric polymers.

Any of the compositions described herein, including the pharmaceuticalcompositions and food products comprising the compositions, may containbacterial strains in any form, for example in an aqueous form, such as asolution or a suspension, embedded in a semi-solid form, in a powderedform or freeze dried form. In some embodiments, the composition or thebacterial strains of the composition are lyophilized. In someembodiments, a subset of the bacterial strains in a composition islyophilized. Methods of lyophilizing compositions, specificallycompositions comprising bacteria, are well known in the art. See, e.g.,U.S. Pat. Nos. 3,261,761; 4,205,132; PCT Publications WO 2014/029578 andWO 2012/098358, herein incorporated by reference in their entirety. Thebacteria may be lyophilized as a combination and/or the bacteria may belyophilized separately and combined prior to administration. A bacterialstrain may be combined with a pharmaceutical excipient prior tocombining it with the other bacterial strain or multiple lyophilizedbacteria may be combined while in lyophilized form and the mixture ofbacteria, once combined may be subsequently be combined with apharmaceutical excipient. In some embodiments, the bacterial strain is alyophilized cake. In some embodiments, the compositions comprising theone or more bacterial strains are a lyophilized cake.

The bacterial strains of the composition can be manufactured usingfermentation techniques well known in the art. In some embodiments, theactive ingredients are manufactured using anaerobic fermenters, whichcan support the rapid growth of anaerobic bacterial species. Theanaerobic fermenters may be, for example, stirred tank reactors ordisposable wave bioreactors. Culture media such as BL media and EGmedia, or similar versions of these media devoid of animal components,can be used to support the growth of the bacterial species. Thebacterial product can be purified and concentrated from the fermentationbroth by traditional techniques, such as centrifugation and filtration,and can optionally be dried and lyophilized by techniques well known inthe art. In some embodiments, the composition of bacterial strains maybe formulated for administration as a pharmaceutical composition. Theterm “pharmaceutical composition” as used herein means a product thatresults from the mixing or combining of at least one active ingredient,such as any two or more purified bacterial strains described herein, andone or more inactive ingredients, which may include one or morepharmaceutically acceptable excipient.

An “acceptable” excipient refers to an excipient that must be compatiblewith the active ingredient and not deleterious to the subject to whichit is administered. In some embodiments, the pharmaceutically acceptableexcipient is selected based on the intended route of administration ofthe composition, for example a composition for oral or nasaladministration may comprise a different pharmaceutically acceptableexcipient than a composition for rectal administration. Examples ofexcipients include sterile water, physiological saline, solvent, a basematerial, an emulsifier, a suspending agent, a surfactant, a stabilizer,a flavoring agent, an aromatic, an excipient, a vehicle, a preservative,a binder, a diluent, a tonicity adjusting agent, a soothing agent, abulking agent, a disintegrating agent, a buffer agent, a coating agent,a lubricant, a colorant, a sweetener, a thickening agent, and asolubilizer.

Pharmaceutical compositions can be prepared in accordance with methodswell known and routinely practiced in the art (see e.g., Remington: TheScience and Practice of Pharmacy, Mack Publishing Co. 20th ed. 2000).The pharmaceutical compositions described herein may further compriseany carriers or stabilizers in the form of a lyophilized formulation oran aqueous solution. Acceptable excipients, carriers, or stabilizers mayinclude, for example, buffers, antioxidants, preservatives, polymers,chelating reagents, and/or surfactants. Pharmaceutical compositions arepreferably manufactured under GMP conditions. The pharmaceuticalcompositions can be used orally, nasally or parenterally, for instance,in the form of capsules, tablets, pills, sachets, liquids, powders,granules, fine granules, film-coated preparations, pellets, troches,sublingual preparations, chewables, buccal preparations, pastes, syrups,suspensions, elixirs, emulsions, liniments, ointments, plasters,cataplasms, transdermal absorption systems, lotions, inhalations,aerosols, injections, suppositories, and the like.

In some embodiments, the bacteria are formulated for delivery to theintestines (e.g., the small intestine and/or the colon). In someembodiments, the bacteria are formulated with an enteric coating thatincreases the survival of the bacteria through the harsh environment inthe stomach. The enteric coating is one which resists the action ofgastric juices in the stomach so that the bacteria which areincorporated therein will pass through the stomach and into theintestines. The enteric coating may readily dissolve when in contactwith intestinal fluids, so that the bacteria enclosed in the coatingwill be released in the intestinal tract. Enteric coatings may consistof polymer and copolymers well known in the art, such as commerciallyavailable EUDRAGIT (Evonik Industries). (See e.g., Zhang, AAPSPharmSciTech, 2016, 17 (1), 56-67).

The bacteria may also be formulated for rectal delivery to the intestine(e.g., the colon). Thus, in some embodiments, the bacterial compositionsmay be formulated for delivery by suppository, colonoscopy, endoscopy,sigmoidoscopy or enema. A pharmaceutical preparation or formulation andparticularly a pharmaceutical preparation for oral administration, mayinclude an additional component that enables efficient delivery of thecompositions of the disclosure to the intestine (e.g., the colon). Avariety of pharmaceutical preparations that allow for the delivery ofthe compositions to the intestine (e.g., the colon) can be used.Examples thereof include pH sensitive compositions, more specifically,buffered sachet formulations or enteric polymers that release theircontents when the pH becomes alkaline after the enteric polymers passthrough the stomach. When a pH sensitive composition is used forformulating the pharmaceutical preparation, the pH sensitive compositionis preferably a polymer whose pH threshold of the decomposition of thecomposition is between about 6.8 and about 7.5. Such a numeric valuerange is a range in which the pH shifts toward the alkaline side at adistal portion of the stomach, and hence is a suitable range for use inthe delivery to the colon. It should further be appreciated that eachpart of the intestine (e.g., the duodenum, jejunum, ileum, cecum, colonand rectum), has different biochemical and chemical environment. Forinstance, parts of the intestines have different pHs, allowing fortargeted delivery by compositions that have a specific pH sensitivity.Thus, the compositions provided herein may be formulated for delivery tothe intestine or specific parts of the intestine (e.g., the duodenum,jejunum, ileum, cecum, colon and rectum) by providing formulations withthe appropriate pH sensitivity. (See e.g., Villena et al., Int J Pharm2015, 487 (1-2): 314-9).

Another embodiment of a pharmaceutical preparation useful for deliveryof the compositions to the intestine (e.g., the colon) is one thatensures the delivery to the colon by delaying the release of thecontents (e.g., the bacterial strains) by approximately 3 to 5 hours,which corresponds to the small intestinal transit time. In oneembodiment of a pharmaceutical preparation for delayed release, ahydrogel is used as a shell. The hydrogel is hydrated and swells uponcontact with gastrointestinal fluid, with the result that the contentsare effectively released (released predominantly in the colon). Delayedrelease dosage units include drug-containing compositions having amaterial which coats or selectively coats a drug or active ingredient tobe administered. Examples of such a selective coating material includein vivo degradable polymers, gradually hydrolyzable polymers, graduallywater-soluble polymers, and/or enzyme degradable polymers. A widevariety of coating materials for efficiently delaying the release isavailable and includes, for example, cellulose-based polymers such ashydroxypropyl cellulose, acrylic acid polymers and copolymers such asmethacrylic acid polymers and copolymers, and vinyl polymers andcopolymers such as polyvinylpyrrolidone.

Additional examples of pharmaceutical compositions that allow for thedelivery to the intestine (e.g., the colon) include bioadhesivecompositions which specifically adhere to the colonic mucosal membrane(for example, a polymer described in the specification of U.S. Pat. No.6,368,586) and compositions into which a protease inhibitor isincorporated for protecting particularly a biopharmaceutical preparationin the gastrointestinal tracts from decomposition due to an activity ofa protease. Another example of a system enabling the delivery to theintestine (e.g., the colon) is a system of delivering a composition tothe colon by pressure change in such a way that the contents arereleased by utilizing pressure change caused by generation of gas inbacterial fermentation at a distal portion of the stomach. Such a systemis not particularly limited, and a more specific example thereof is acapsule which has contents dispersed in a suppository base and which iscoated with a hydrophobic polymer (for example, ethyl cellulose). Afurther example of a system enabling the delivery of a composition tothe intestine (e.g., the colon), is a composition that includes acoating that can be removed by an enzyme present in the gut (e.g., thecolon), such as, for example, a carbohydrate hydrolase or a carbohydratereductase. Such a system is not particularly limited, and more specificexamples thereof include systems which use food components such asnon-starch polysaccharides, amylose, xanthan gum, and azopolymers.

The compositions provided herein can also be delivered to specifictarget areas, such as the intestine, by delivery through an orifice(e.g., a nasal tube) or through surgery. In addition, the compositionsprovided herein that are formulated for delivery to a specific area(e.g., the cecum or the colon), may be administered by a tube (e.g.,directly into the small intestine). Combining mechanical deliverymethods such as tubes with chemical delivery methods such as pH specificcoatings, allow for the delivery of the compositions provided herein toa desired target area (e.g., the cecum or the colon). The compositionscomprising bacterial strains are formulated into pharmaceuticallyacceptable dosage forms by conventional methods known to those of skillin the art. Dosage regimens are adjusted to provide the optimum desiredresponse (e.g., the prophylactic or therapeutic effect). In someembodiments, the dosage form of the composition is a tablet, pill,capsule, powder, granules, solution, or suppository. In someembodiments, the pharmaceutical composition is formulated for oraladministration. In some embodiments, the pharmaceutical composition isformulated such that the bacteria of the composition, or a portionthereof, remain viable after passage through the stomach of the subject.In some embodiments, the pharmaceutical composition is formulated forrectal administration, e.g. as a suppository. In some embodiments, thepharmaceutical composition is formulated for delivery to the intestineor a specific area of the intestine (e.g., the colon) by providing anappropriate coating (e.g., a pH specific coating, a coating that can bedegraded by target area specific enzymes, or a coating that can bind toreceptors that are present in a target area).

Dosages of the active ingredients in the pharmaceutical compositions canbe varied so as to obtain an amount of the active ingredient which iseffective to achieve the desired pharmaceutical response for aparticular subject, composition, and mode of administration, withoutbeing toxic or having an adverse effect on the subject. The selecteddosage level depends upon a variety of factors including the activity ofthe particular compositions employed, the route of administration, thetime of administration, the duration of the treatment, other drugs,compounds and/or materials used in combination with the particularcompositions employed, the age, sex, weight, condition, general healthand prior medical history of the subject being treated, and likefactors.

A physician, veterinarian or other trained practitioner, can start dosesof the pharmaceutical composition at levels lower than that required toachieve the desired therapeutic effect and gradually increase the dosageuntil the desired effect (e.g., treatment of a pathogenic infection,reduction of bacterial burden of pathogenic infection, reduction orinhibition of toxin production) is achieved. In general, effective dosesof the compositions disclosed herein, for the prophylactic treatment ofgroups of people as described herein vary depending upon many differentfactors, including routes of administration, physiological state of thesubject, whether the subject is human or an animal, other medicationsadministered, and the therapeutic effect desired. Dosages need to betitrated to optimize safety and efficacy. In some embodiments, thedosing regimen entails oral administration of a dose of any of thecompositions described herein. In some embodiments, the dosing regimenentails oral administration of multiple doses of any of the compositionsdescribed herein. In some embodiments, the composition is administeredorally the subject once, twice, 3 times, 4 times, 5 times, 6 times, 7times, 8 times, 9 times, or at least 10 times.

The compositions, including the pharmaceutical compositions disclosedherein, include compositions with a range of active ingredients (e.g.,live bacteria, bacteria in spore format). The amount of bacteria in thecompositions may be expressed in weight, number of bacteria and/or CFUs(colony forming units). In some embodiments, the pharmaceuticalcompositions disclosed herein contain about 10, about 10², about 10³,about 10⁴, about 10⁵, about 10⁶, about 10⁷, about 10⁸, about 10⁹, about10¹⁰, about 10¹¹, about 10¹², about 10¹³ or more of each of the bacteriaof the composition per dosage amount. In some embodiments, thepharmaceutical compositions disclosed herein contain about 10, about10², about 10³, about 10⁴, about 10⁵, about 10⁶, about 10⁷, about 10⁸,about 10⁹, about 10¹⁰, about 10¹¹, about 10¹², about 10¹³ or more totalbacteria per dosage amount. It should further be appreciated that thebacteria of the compositions may be present in different amounts. Thus,for instance, as a non-limiting example, a composition may include 10³of bacteria A, 10⁴ of bacteria B and 10⁶ of bacteria C. In someembodiments, the pharmaceutical compositions disclosed herein containabout 10, about 10², about 10³, about 10⁴, about 10⁵, about 10⁶, about10⁷, about 10⁸, about 10⁹, about 10¹⁰, about 10¹¹, about 10¹², about10¹³ or more CFUs of each of the bacteria in the composition per dosageamount. In some embodiments, the pharmaceutical compositions disclosedherein contain about 10¹, about 10², about 10³, about 10⁴, about 10⁵,about 10⁶, about 10⁷, about 10⁸, about 10⁹, about 10¹⁰, about 10¹¹,about 10¹², about 10¹³ or more CFUs in total for all of the bacteriacombined per dosage amount. As discussed above, bacteria of thecompositions may be present in different amounts. In some embodiments,the pharmaceutical compositions disclosed herein contain about 10⁻⁷,about 10⁻⁶, about 10⁻⁵, about 10⁻⁴, about 10⁻³, about 10⁻², about 10⁻¹or more grams of each of the bacteria in the composition per dosageamount. In some embodiments, the pharmaceutical compositions disclosedherein contain about 10⁻⁷, about 10⁻⁶, about 10⁻⁵, about 10⁻⁴, about10⁻³, about 10⁻², about 10⁻¹ or more grams in total for all of thebacteria combined per dosage amount. In some embodiment, the dosageamount is one administration device (e.g., one table, pill or capsule).In some embodiment, the dosage amount is the amount that is administeredin a particular period (e.g., one day or one week).

In some embodiments, the pharmaceutical compositions disclosed hereincontain between 10 and 10¹³, between 10² and 10¹³, between 10³ and 10¹³,between 10⁴ and 10¹³, between 10⁵ and 10¹³, between 10⁶ and 10¹³,between 10⁷ and 10¹³, between 10⁸ and 10¹³, between 10⁹ and 10¹³,between 10¹⁰ and 10¹³, between 10¹¹ and 10¹³, between 10¹² and 10¹³,between 10 and 10¹², between 10² and 10¹², between 10³ and 10¹², between10⁴ and 10¹², between 10⁵ and 10¹², between 10⁶ and 10¹², between 10⁷and 10¹², between 10⁸ and 10¹², between 10⁹ and 10¹², between 10¹⁰ and10¹², between 10¹¹ and 10¹², between 10 and 10¹¹, between 10² and 10¹¹,between 10³ and 10¹³, between 10⁴ and 10¹³, between 10⁵ and 10¹³,between 10⁶ and 10¹³, between 10⁷ and 10¹¹, between 10⁸ and 10¹¹,between 10⁹ and 10¹¹, between 10¹⁰ and 10¹¹, between 10 and 10¹⁰,between 10² and 10¹⁰, between 10³ and 10¹⁰, between 10⁴ and 10¹⁰,between 10⁵ and 10¹⁰, between 10⁶ and 10¹⁰, between 10⁷ and 10¹⁰,between 10⁸ and 10¹⁰, between 10⁹ and 10¹⁰, between 10 and 10⁹, between10² and 10⁹, between 10³ and 10⁹, between 10⁴ and 10⁹, between 10⁵ and10⁹, between 10⁶ and 10⁹, between 10⁷ and 10⁹, between 10⁸ and 10⁹,between 10 and 10⁸, between 10² and 10⁸, between 10³ and 10⁸, between10⁴ and 10⁸, between 10⁵ and 10⁸, between 10⁶ and 10⁸, between 10⁷ and10⁸, between 10 and 10⁷, between 10² and 10⁷, between 10³ and 10⁷,between 10⁴ and 10⁷, between 10⁵ and 10⁷, between 10⁶ and 10⁷, between10 and 10⁶, between 10² and 10⁶, between 10³ and 10⁶, between 10⁴ and10⁶, between 10⁵ and 10⁶, between 10 and 10⁵, between 10² and 10⁵,between 10³ and 10⁵, between 10⁴ and 10⁵, between 10 and 10⁴, between10² and 10⁴, between 10³ and 10⁴, between 10 and 10³, between 10² and10³, or between 10 and 10² of each of the bacteria of the compositionper dosage amount. In some embodiments, the pharmaceutical compositionsdisclosed herein contain between 10 and 10¹³, between 10² and 10¹³,between 10³ and 10¹³, between 10⁴ and 10¹³, between 10⁵ and 10¹³,between 10⁶ and 10¹³, between 10⁷ and 10¹³, between 10⁸ and 10¹³,between 10⁹ and 10¹³, between 10¹⁰ and 10¹³, between 10¹¹ and 10¹³,between 10¹² and 10¹³, between 10 and 10¹², between 10² and 10¹²,between 10³ and 10¹², between 10⁴ and 10¹², between 10⁵ and 10¹²,between 10⁶ and 10¹², between 10⁷ and 10¹², between 10⁸ and 10¹²,between 10⁹ and 10¹², between 10¹⁰ and 10¹², between 10¹¹ and 10¹²,between 10 and 10¹¹, between 10² and 10¹¹, between 10³ and 10¹³, between10⁴ and 10¹³, between 10⁵ and 10¹³, between 10⁶ and 10¹³, between 10⁷and 10¹¹, between 10⁸ and 10¹¹, between 10⁹ and 10¹¹, between 10¹⁰ and10¹¹, between 10 and 10¹⁰, between 10² and 10¹⁰, between 10³ and 10¹⁰,between 10⁴ and 10¹⁰, between 10⁵ and 10¹⁰, between 10⁶ and 10¹⁰,between 10⁷ and 10¹⁰, between 10⁸ and 10¹⁰, between 10⁹ and 10¹⁰,between 10 and 10⁹, between 10² and 10⁹, between 10³ and 10⁹, between10⁴ and 10⁹, between 10⁵ and 10⁹, between 10⁶ and 10⁹, between 10⁷ and10⁹, between 10⁸ and 10⁹, between 10 and 10⁸, between 10² and 10⁸,between 10³ and 10⁸, between 10⁴ and 10⁸, between 10⁵ and 10⁸, between10⁶ and 10⁸, between 10⁷ and 10⁸, between 10 and 10⁷, between 10² and10⁷, between 10³ and 10⁷, between 10⁴ and 10⁷, between 10⁵ and 10⁷,between 10⁶ and 10⁷, between 10 and 10⁶, between 10² and 10⁶, between10³ and 10⁶, between 10⁴ and 10⁶, between 10⁵ and 10⁶, between 10 and10⁵, between 10² and 10⁵, between 10³ and 10⁵, between 10⁴ and 10⁵,between 10 and 10⁴, between 10² and 10⁴, between 10³ and 10⁴, between 10and 10³, between 10² and 10³, or between 10 and 10² total bacteria perdosage amount.

In some embodiments, the pharmaceutical compositions disclosed hereincontain between 10 and 10¹³, between 10² and 10¹³, between 10³ and 10¹³,between 10⁴ and 10¹³, between 10⁵ and 10¹³, between 10⁶ and 10¹³,between 10⁷ and 10¹³, between 10⁸ and 10¹³, between 10⁹ and 10¹³,between 10¹⁰ and 10¹³, between 10¹¹ and 10¹³, between 10¹² and 10¹³,between 10 and 10¹², between 10² and 10¹², between 10³ and 10¹², between10⁴ and 10¹², between 10⁵ and 10¹², between 10⁶ and 10¹², between 10⁷and 10¹², between 10⁸ and 10¹², between 10⁹ and 10¹², between 10¹⁰ and10¹², between 10¹¹ and 10¹², between 10 and 10¹¹, between 10² and 10¹¹,between 10³ and 10¹³, between 10⁴ and 10¹³, between 10⁵ and 10¹³,between 10⁶ and 10¹³, between 10⁷ and 10¹¹, between 10⁸ and 10¹¹,between 10⁹ and 10¹¹, between 10¹⁰ and 10¹¹, between 10 and 10¹⁰,between 10² and 10¹⁰, between 10³ and 10¹⁰, between 10⁴ and 10¹⁰,between 10⁵ and 10¹⁰, between 10⁶ and 10¹⁰, between 10⁷ and 10¹⁰,between 10⁸ and 10¹⁰, between 10⁹ and 10¹⁰, between 10 and 10⁹, between10² and 10⁹, between 10³ and 10⁹, between 10⁴ and 10⁹, between 10⁵ and10⁹, between 10⁶ and 10⁹, between 10⁷ and 10⁹, between 10⁸ and 10⁹,between 10 and 10⁸, between 10² and 10⁸, between 10³ and 10⁸, between10⁴ and 10⁸, between 10⁵ and 10⁸, between 10⁶ and 10⁸, between 10⁷ and10⁸, between 10 and 10⁷, between 10² and 10⁷, between 10³ and 10⁷,between 10⁴ and 10⁷, between 10⁵ and 10⁷, between 10⁶ and 10⁷, between10 and 10⁶, between 10² and 10⁶, between 10³ and 10⁶, between 10⁴ and10⁶, between 10⁵ and 10⁶, between 10 and 10⁵, between 10² and 10⁵,between 10³ and 10⁵, between 104 and 105, between 10 and 104, between102 and 104, between 10³ and 10⁴, between 10 and 10³, between 10² and10³, or between 10 and 10² CFUs of each of the bacteria of thecomposition per dosage amount. In some embodiments, the pharmaceuticalcompositions disclosed herein contain between 10 and 10¹³, between 10²and 10¹³, between 10³ and 10¹³, between 10⁴ and 10¹³, between 10⁵ and10¹³, between 10⁶ and 10¹³, between 10⁷ and 10¹³, between 10⁸ and 10¹³,between 10⁹ and 10¹³, between 10¹⁰ and 10¹³, between 10¹¹ and 10¹³,between 10¹² and 10¹³, between 10 and 10¹², between 10² and 10¹²,between 10³ and 10¹², between 10⁴ and 10¹², between 10⁵ and 10¹²,between 10⁶ and 10¹², between 10⁷ and 10¹², between 10⁸ and 10¹²,between 10⁹ and 10¹², between 10¹⁰ and 10¹², between 10¹¹ and 10¹²,between 10 and 10¹¹, between 10² and 10¹¹, between 10³ and 10¹³, between10⁴ and 10¹³, between 10⁵ and 10¹³, between 10⁶ and 10¹³, between 10⁷and 10¹¹, between 10⁸ and 10¹¹, between 10⁹ and 10¹¹, between 10¹⁰ and10¹¹, between 10 and 10¹⁰, between 10² and 10¹⁰, between 10³ and 10¹⁰,between 10⁴ and 10¹⁰, between 10⁵ and 10¹⁰, between 10⁶ and 10¹⁰,between 10⁷ and 10¹⁰, between 10⁸ and 10¹⁰, between 10⁹ and 10¹⁰,between 10 and 10⁹, between 10² and 10⁹, between 10³ and 10⁹, between10⁴ and 10⁹, between 10⁵ and 10⁹, between 10⁶ and 10⁹, between 10⁷ and10⁹, between 10⁸ and 10⁹, between 10 and 10⁸, between 10² and 10⁸,between 10³ and 10⁸, between 10⁴ and 10⁸, between 10⁵ and 10⁸, between10⁶ and 10⁸, between 10⁷ and 10⁸, between 10 and 10⁷, between 10² and10⁷, between 10³ and 10⁷, between 10⁴ and 10⁷, between 10⁵ and 10⁷,between 10⁶ and 10⁷, between 10 and 10⁶, between 10² and 10⁶, between10³ and 10⁶, between 10⁴ and 10⁶, between 10⁵ and 10⁶, between 10 and10⁵, between 10² and 10⁵, between 10³ and 10⁵, between 10⁴ and 10⁵,between 10 and 10⁴, between 10² and 10⁴, between 10³ and 10⁴, between 10and 10³, between 10² and 10³, or between 10 and 10² total CFUs perdosage amount.

In some embodiments, the pharmaceutical compositions disclosed hereincontain between 10⁻⁷ and 10⁻¹, between 10⁻⁶ and 10⁻¹, between 10⁻⁵ and10⁻¹, between 10⁻⁴ and 10⁻¹, between 10⁻³ and 10⁻¹, between 10⁻² and10⁻¹, between 10⁻⁷ and 10⁻², between 10⁻⁶ and 10⁻², between 10⁻⁵ and10⁻², between 10⁻⁴ and 10⁻², between 10⁻³ and 10⁻², between 10⁻⁷ and10⁻³, between 10⁻⁶ and 10⁻³, between 10⁻⁵ and 10⁻³, between 10⁻⁴ and10⁻³, between 10⁻⁷ and 10⁻⁴, between 10⁻⁶ and 10⁻⁴, between 10⁻⁵ and10⁻⁴, between 10⁻⁷ and 10⁻⁵, between 10⁻⁶ and 10⁻⁵, or between 10⁻⁷ and10⁻⁶ grams of each of the bacteria in the composition per dosage amount.In some embodiments, the pharmaceutical compositions disclosed hereincontain between 10⁻⁷ and 10⁻¹, between 10⁻⁶ and 10⁻¹, between 10⁻⁵ and10⁻¹, between 10⁻⁴ and 10⁻¹, between 10⁻³ and 10⁻¹, between 10⁻² and10⁻¹, between 10⁻⁷ and 10⁻², between 10⁻⁶ and 10⁻², between 10⁻⁵ and10⁻², between 10⁻⁴ and 10⁻², between 10⁻³ and 10⁻², between 10⁻⁷ and10⁻³, between 10⁻⁶ and 10⁻³, between 10⁻⁵ and 10⁻³, between 10⁻⁴ and10⁻³, between 10⁻⁷ and 10⁻⁴, between 10⁻⁶ and 10⁻⁴, between 10⁻⁵ and10⁻⁴, between 10⁻⁷ and 10⁻⁵, between 10⁻⁶ and 10⁻⁵, or between 10⁻⁷ and10⁻⁶ grams of all of the bacteria combined per dosage amount.

In one aspect, the disclosure provides a food product comprising any ofthe compositions provided herein and a nutrient. Also with the scope ofthe present disclosure are food products comprising any of the bacterialstrains described herein and a nutrient. Food products are, in general,intended for the consumption of a human or an animal. Any of thebacterial strains described herein may be formulated as a food product.In some embodiments, the bacterial strains are formulated as a foodproduct in spore form. In some embodiments, the bacterial strains areformulated as a food product in vegetative form. In some embodiments,the food product comprises both vegetative bacteria and bacteria inspore form. The compositions disclosed herein can be used in a food orbeverage, such as a health food or beverage, a food or beverage forinfants, a food or beverage for pregnant women, athletes, seniorcitizens or other specified group, a functional food, a beverage, a foodor beverage for specified health use, a dietary supplement, a food orbeverage for patients, or an animal feed. Non-limiting examples of thefoods and beverages include various beverages such as juices, refreshingbeverages, tea beverages, drink preparations, jelly beverages, andfunctional beverages; alcoholic beverages such as beers;carbohydrate-containing foods such as rice food products, noodles,breads, and pastas; paste products such as fish hams, sausages, pasteproducts of seafood; retort pouch products such as curries, food dressedwith a thick starchy sauces, soups; dairy products such as milk, dairybeverages, ice creams, cheeses, and yogurts; fermented products such asfermented soybean pastes, yogurts, fermented beverages, and pickles;bean products; various confectionery products such as Westernconfectionery products including biscuits, cookies, and the like,Japanese confectionery products including steamed bean-jam buns, softadzuki-bean jellies, and the like, candies, chewing gums, gummies, colddesserts including jellies, cream caramels, and frozen desserts; instantfoods such as instant soups and instant soy-bean soups; microwavablefoods; and the like. Further, the examples also include health foods andbeverages prepared in the forms of powders, granules, tablets, capsules,liquids, pastes, and jellies.

Food products containing bacterial strains described herein may beproduced using methods known in the art and may contain the same amountof bacteria (e.g., by weight, amount or CFU) as the pharmaceuticalcompositions provided herein. Selection of an appropriate amount ofbacteria in the food product may depend on various factors, includingfor example, the serving size of the food product, the frequency ofconsumption of the food product, the specific bacterial strainscontained in the food product, the amount of water in the food product,and/or additional conditions for survival of the bacteria in the foodproduct. Examples of food products which may be formulated to containany of the bacterial strains described herein include, withoutlimitation, a beverage, a drink, a bar, a snack, a dairy product, aconfectionery product, a cereal product, a ready-to-eat product, anutritional formula, such as a nutritional supplementary formulation, afood or beverage additive.

In some embodiments, the subject has not received a dose of anantibiotic prior to administration of the bacterial composition. In someembodiments, the subject has not been administered an antibiotic atleast 1, at least 2, at least 3, at least 5, at least 10, at least 15,at least 20, at least 25, at least 30, at least 60, at least 90, atleast 120, at least 180 or at least 360 days prior to administration ofthe compositions provided herein. In some embodiments, the subject maybe administered one or more doses of an antibiotic prior to orconcurrently with a bacterial composition. Antibiotics may beadministered for a variety of reasons. For instance, antibiotics may beadministered to remove bacterial species from the colon and/or intestineprior to administration of the bacterial compositions provided herein.Antibiotics may also be administered to suppress unwanted infections inthe case of cancer treatment. In some instances, antibiotics may beadministered as a treatment method for an infectious disease. In someembodiments, the subject is administered a single dose of an antibioticprior to the bacterial composition. In some embodiments, the subject isadministered multiple doses of an antibiotic prior to the bacterialcomposition. In some embodiments, the subject is administered at least2, 3, 4, 5 or more doses of an antibiotic prior to the bacterialcomposition. In some embodiments, the subject is administered a dose ofan antibiotic at substantially the same time as the bacterialcomposition. Examples of antibiotics that can be administered include,without limitation, kanamycin, gentamicin, colistin, metronidazole,vancomycin, clindamycin, fidaxomicin, and cefoperazone.

Diagnostics and Prognostic Methods

Also described herein are diagnostic methods (e.g., companiondiagnostics) for use in determining whether a subject should receive atreatment, such as a composition as described herein and/or any of theimmune checkpoint inhibitors described herein. Such methods can be usedfor diagnosing a disease, monitoring the progress of a disease,assessing the efficacy of a treatment for the disease, and/oridentifying patients suitable for a particular treatment. Accordingly,the methods described herein are based on the level of a marker in asample (e.g., a biological sample containing lymphocytes) obtained froma subject. In some embodiments, the methods involve analyzing thepresence and/or level of a marker in one or more samples from a subject.

In some embodiments, the level of the marker in a sample obtained from asubject can then be compared with a reference sample or a control sampleto determine a value indicating the amount of the marker in the sample.In some embodiments, a value for a marker is obtained by comparing thelevel of a marker in a sample to the level of another marker (e.g., aninternal control or internal standard) in the sample. The value of themarker can be compared to a reference value to determine whether thesubject has or is at risk for the disease. In some embodiments, thelevel of the marker is compared to a predetermined threshold for themarker, a deviation from which may indicate the subject has a disease.In some embodiments, if the level or value of the marker is higher thana reference level or value, the subject can be identified as having orat risk for a disease, as described herein. In some embodiments, if thelevel or value of the marker is lower than a reference level or value,the subject can be identified as having or at risk for a disease, asdescribed herein. In some embodiments, the level of the marker in asample from a subject is compared to the level of the marker in anothersample obtained from the same subject, for example, a sample obtainedfrom the subject at a different time. In some embodiments, the level ofthe marker in a sample from a subject is compared to the level of themarker in a sample obtained from the subject at an earlier time, such asprior to administration of any of the compositions described herein. Insome embodiments, the level of the marker in a sample from a subject iscompared to the level of the marker in a sample obtained from thesubject at a later time, such as after administration of any of thecompositions described herein.

In some embodiments, if the level or value of the marker is higher in asample as compared to the level or value of the marker in a sample fromthe subject obtained prior to administration of a composition describedherein, the subject is administered an immune checkpoint inhibitor and acomposition described herein. In some embodiments, if the level or valueof the marker is higher in a sample as compared to the level or value ofthe marker in a sample from the subject obtained prior to administrationof a composition described herein, the subject continues a therapyinvolving administration of an immune checkpoint inhibitor and acomposition described herein. In some embodiments, the level or value ofthe marker in a sample is enhanced at least 10%, 15%, 20%, 25%, 30%,35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%,110%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190%, or at least 200%as compared the level of value of the marker in a sample prior toadministration of a composition as described herein.

In some embodiments, if the level or value of the marker is notincreased (e.g., equal to or lower) in a sample as compared to the levelor value of the marker in a sample from the subject obtained prior toadministration of a composition described herein, administration of animmune checkpoint inhibitor and a composition described herein isdiscontinued. In some embodiments, if the level or value of the markeris not increased (e.g., equal to or lower) in a sample as compared tothe level or value of the marker in a sample from the subject obtainedprior to administration of a composition described herein, theadministration of an immune checkpoint inhibitor and a compositiondescribed herein is reanalyzed after administration of a composition asdescribed herein. In some embodiments, the level or value of the markerin a sample is reduced at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%,50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 110%, 120%,130%, 140%, 150%, 160%, 170%, 180%, 190%, or at least 200% as comparedthe level of value of the marker in a sample prior to administration ofa composition as described herein. In some embodiments, the level of themarker is determined by analyzing the expression of the marker (e.g.,protein or nucleic acid level) and/or the cell type in which the markeris expressed. Any method known the art may be used to analyze theexpression of the marker and/or cell type in which the marker isexpressed.

Also provided herein are methods based on the level or degree of IFNγproduction in a sample (e.g., a biological sample containingsplenocytes) obtained from a subject. In some embodiments, the methodsinvolve analyzing the presence and/or level of IFN production in one ormore samples from a subject. In some embodiments, the level of IFNγproduction in a sample obtained from a subject can then be compared witha reference sample or a control sample to determine a value indicatingthe amount of the IFNγ production in the sample. In some embodiments, avalue for IFNγ production is obtained by comparing the level of IFNproduction in a sample to the level of another molecule (e.g., aninternal control or internal standard) in the sample. The value of IFNγproduction can be compared to a reference value to determine whether thesubject has or is at risk for the disease. In some embodiments, thelevel of IFNγ production is compared to a predetermined threshold forIFNγ production, a deviation from which may indicate the subject has adisease. In some embodiments, if the level or value of IFNγ productionis higher than a reference level or value, the subject can be identifiedas having or at risk for a disease, as described herein. In someembodiments, if the level or value of IFNγ production is lower than areference level or value, the subject can be identified as having or atrisk for a disease, as described herein.

In some embodiments, the level of IFNγ production in a sample from asubject is compared to the level of IFNγ production in another sampleobtained from the same subject, for example, a sample obtained from thesubject at a different time. In some embodiments, the level of IFNγproduction in a sample from a subject is compared to the level of IFNγproduction in a sample obtained from the subject at an earlier time,such as prior to administration of any of the compositions describedherein. In some embodiments, the level of IFNγ production in a samplefrom a subject is compared to the level of IFNγ production in a sampleobtained from the subject at a later time, such as after administrationof any of the compositions described herein. In some embodiments, if thelevel or value of IFNγ production is higher in a sample as compared tothe level or value of IFNγ production in a sample from the subjectobtained prior to administration of a composition described herein, thesubject is administered an immune checkpoint inhibitor and a compositiondescribed herein. In some embodiments, if the level or value of IFNγproduction is higher in a sample as compared to the level or value ofIFNγ production in a sample from the subject obtained prior toadministration of a composition described herein, the subject continuesa therapy involving administration of an immune checkpoint inhibitor anda composition described herein. In some embodiments, the level or valueof IFN production in a sample is enhanced at least 10%, 15%, 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%,100%, 110%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190%, or at least200% as compared the level of value of IFNγ production in a sample priorto administration of a composition as described herein.

In some embodiments, if the level or value of IFNγ production is notincreased (e.g., equal to or lower) in a sample as compared to the levelor value of IFNγ production in a sample from the subject obtained priorto administration of a composition described herein, administration ofan immune checkpoint inhibitor and a composition described herein isdiscontinued. In some embodiments, if the level or value of IFNγproduction is not increased (e.g., equal to or lower) in a sample ascompared to the level or value of IFNγ production in a sample from thesubject obtained prior to administration of a composition describedherein, the administration of an immune checkpoint inhibitor and acomposition described herein is reanalyzed after administration of acomposition as described herein. In some embodiments, the level or valueof IFNγ production in a sample is reduced at least 10%, 15%, 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%,100%, 110%, 120%, 130%, 140%, 150%, 160%, 170%, 180%, 190%, or at least200% as compared the level of value of IFNγ production in a sample priorto administration of a composition as described herein.

In some embodiments, the level of IFNγ production is determined byanalyzing the expression of IFNγ (e.g., protein or nucleic acid level)and/or the cell type by which IFNγ is produced. Any method known the artmay be used to analyze the expression of IFNγ and/or identify the celltype that produces IFNγ. The control level can also be a predeterminedlevel or threshold. Such a predetermined level can represent the levelof the marker or IFNγ production in a population of subjects that do nothave or are not at risk for the target disease. It can also representthe level of the marker or IFNγ production in a population of subjectsthat have the target disease. The predetermined level can take a varietyof forms. For example, it can be single cut-off value, such as a medianor mean. In some embodiments, such a predetermined level can beestablished based upon comparative groups, such as where one definedgroup is known to have a target disease and another defined group isknown to not have the target disease. Alternatively, the predeterminedlevel can be a range, for example, a range representing the levels ofthe metabolite in a control population.

As used herein, “an elevated level” or “an increased level” means thatthe level of the marker or IFNγ production is higher than a referencevalue or the level in another sample, such as a sample obtained from thesubject prior to administration of any of the compositions describedherein. An elevated level of a marker or IFNγ production includes alevel of the marker or IFNγ production that is, for example, 1%, 5%,10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 150%, 200%, 300%,400%, 500% or more above a reference value or above the level in anothersample from the subject. In some embodiments, the level of the marker orIFNγ production in the test sample is at least 1.1, 1.2, 1.3, 1.4, 15,1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, 10, 50,100, 150, 200, 300, 400, 500, 1000, 10000-fold or more, higher than thelevel in a reference sample or the level in another sample from thesubject. As used herein, “a decreased level” means that the level of themarker or IFNγ production is lower than a reference value or the levelin another sample, such as a sample obtained from the subject prior toadministration of any of the compositions described herein. A decreasedlevel of the marker or IFNγ production includes a level of the marker orIFNγ production that is, for example, 1%, 5%, 10%, 20%, 30%, 40%, 50%,60%, 70%, 80%, 90%, 100%, 150%, 200%, 300%, 400%, 500% or more lowerthan a reference value or the level in another sample from the subject.In some embodiments, the level of the marker or IFNγ production in thetest sample is at least 1.1, 1.2, 1.3, 1.4, 15, 1.6, 1.7, 1.8, 1.9, 2,2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9, 10, 50, 100, 150, 200, 300,400, 500, 1000, 10000-fold or more lower than the level of the marker orIFNγ production in a reference sample or the level in another samplefrom the subject.

A subject identified in the methods described herein may be subject to asuitable treatment, such as treatment with a combination of an immunecheckpoint inhibitor and any of the composition, as described herein.The assay methods and kits described herein also can be applied forevaluation of the efficacy of a treatment for a disease, such as thosedescribed herein, given the correlation between the level of the markeror IFNγ production and such diseases. For examples, multiple biologicalsamples can be collected from a subject to whom a treatment is performedeither before and after the treatment or during the course of thetreatment. The levels of a marker or IFNγ production may be indicativeas to whether the treatment is effective. If the subject is identifiedas not responsive to the treatment, a higher dose and/or frequency ofdosage of the composition and/or immune checkpoint inhibitors areadministered to the subject identified. In some embodiments, the dosageor frequency of dosage of the therapeutic agent is maintained, lowered,or ceased in a subject identified as responsive to the treatment or notin need of further treatment. Alternatively, a different treatment canbe applied to the subject who is found as not responsive to the firsttreatment. In other embodiments, the values of a marker or IFNγproduction can also be relied on to identify a disease may be treatable,for example by administering the compositions described herein.

Screening Methods

Provided herein are methods for screening bacteria or physiologicallyactive substances derived from bacteria to identify bacteria orphysiologically active substances thereof that produce a desiredresponse. For example, in some embodiments, the screening methods areused to identify bacteria or physiologically active substances derivedfrom bacteria that induce activation of CD8+ IFNγ-producing T cells. Insome embodiments, the screening methods are used to identify bacteria orphysiologically active substances derived from bacteria that induceactivation of CD8+ IFNγ-producing T cells. In some embodiments, thescreening methods are used to identify bacteria or physiologicallyactive substances derived from bacteria as an immunostimulatory agent.Also provided herein are methods for screening test substances toidentify substances that induce activation induce or exacerbate adisease caused by CD8+ IFNγ-producing T cells. In general, the screeningmethods may be performed in vitro (e.g., using cells) or in vivo (e.g.,using non-human animal models). In some embodiments, the methods involvecontacting a population of cells (e.g., intestinal epithelial cells,peripheral blood mononuclear cells) with a test substance (e.g.,bacteria or physiologically active substances thereof) and assessing aresponse. In some embodiments, the response is the number and/oractivity of a desired cell population (e.g., CD8+ IFNγ T cells).

In some embodiments, the methods involve inoculating a non-human animalmodel with a test substance (e.g., bacteria or physiologically activesubstances thereof) and assessing a response. In some embodiments, thenon-human animal model ingests the test substance. In some embodiments,the response is the number and/or activity of a desired cell population(e.g., CD8+ IFNγ T cells). In some embodiments, the response is animprovement of a disease or symptom thereof, or induction/exacerbationof a disease or symptom thereof.

In some embodiments, the bacteria and/or the physiologically activesubstances derived from bacteria identified in any of the screeningmethods described herein may be administered to a subject, for examplefor the treatment of a disease.

Kits

The present disclosure also provides kits for use in evaluating theimmune system activation, for example based on the degree or level ofIFNγ production in splenocytes, involving administering to a subject anyof the compositions as described herein. In some embodiments, a samplemay be obtained from the subject prior to, during, and/or afteradministration of any of the compositions described herein. In someembodiments, the kit contains one or more molecules for detecting and/ormeasuring the amount of IFNγ production in a sample. In someembodiments, the molecule that detects or measures the amount of IFNγproduction can comprise one or more binding agents that specificallybind to IFNγ. In some embodiments, the binding agent is an antibody thatspecifically binds to IFNγ. In some embodiments, the binding agent ispart of a reporter system, such as a receptor on a cell that binds tothe IFNγ and induces expression of a gene encoding a reporter molecule.In some embodiments, the kit also contains a standard or control sampleto which the amount of IFNγ in the sample(s) obtained from the subjectmay be compared.

In some embodiments, the kit may be for carrying out any of thecompanion diagnostic methods described herein. In some embodiments, thekit contains one or more molecules for detecting and/or measuring theamount or presence of any one of the bacterial species described herein,or component thereof. In some embodiments, the molecule that detects ormeasures the amount of a bacterial strain can comprise one or morebinding agents that specifically bind to the bacterial strain. In someembodiments, the binding agent specifically binds to a feature of one ormore bacterial species that identifies the bacterial species. In someembodiments, the binding agent is a nucleic acid that specifically bindsto a nucleic acid sequence of one or more of the bacterial speciesdescribed herein, such as a specific 16S rRNA sequence. In someembodiments, the kit also contains a standard or control sample to whichthe sample(s) obtained from the subject may be compared.

The present disclosure also provides kits for use in determining atreatment method, for example, a tumor therapy, involving analyzing theexpression of a marker (e.g., CD44, CD8, IFNγ, GzmB, gp70 MC38 peptide(KSPWFTTL; (SEQ ID NO: 53))-specific TCRβ, or an antigen-derivedligand-specific TCRβ), prior to, during, and/or after administration ofany of the compositions described herein. Also provided herein are kitscomprising companion diagnostics for tumor therapy with an immunecheckpoint inhibitor (e.g., a PD-1 inhibitor). In some embodiments, thekit includes one or more components for analyzing or monitoringexpression levels of a marker, such as CD44, CD8, IFNγ, GzmB, or a tumorantigen-derived ligand-specific TCRβ. In some embodiments, the marker isanalyzed by detecting the presence of the marker, by measuring the level(amount) of the marker, and/or a specific cell type on which the markeris presented. In some embodiments, the molecule that detects or measuresthe amount of the marker can comprise one or more binding agents thatspecifically bind to the marker. In some embodiments, the binding agentis an antibody that specifically binds to the marker. In someembodiments, the binding agent is an MHC multimer that specificallybinds to the marker.

In some embodiments, the marker is analyzed by detecting the presence ofa nucleic acid encoding the marker, by measuring the level (amount) of anucleic acid encoding the marker, and/or a specific cell type in whichthe nucleic acid encoding the marker is expressed. In some embodiments,the kit includes one or more reagents for the isolation of nucleic acids(e.g., RNA) from a sample obtained from subject. In some embodiments,the kits further comprise a detection agent (e.g., an antibody bindingto the binding agent) for detecting binding of the agent to the target(e.g., IFNγ, bacterial species) in the sample. The detection agent canbe conjugated to a label. In some embodiments, the detection agent is anantibody that specifically binds to at least one of the binding agents.In some embodiments, the binding agent comprises a tag that can beidentified and, directly or indirectly, bound by a detection agent.

In some embodiments, the kit may further include one or moretherapeutics and/or compositions for administering to the subject. Forexample, in some embodiments, the kit may include one or more immunecheckpoint inhibitor (e.g., PD-1 inhibitor, PD-L1 inhibitor, CTLA-4inhibitor). In some embodiments, the kit may include a compositioncomprising one or more of the bacterial strains described herein. Insome embodiments, the kits may be for screening bacteria or substancesderived from bacteria, for example of activation of CD8+ IFNγ-producingT cells. In some embodiments, the kits include cells, such as cells of acell line. In some embodiments, the cells are intestinal epithelialcells, peripheral blood mononuclear cells. In some embodiments, the kitor device further includes a support member. In some embodiments, thesupport member is a membrane, such as a nitrocellulose membrane, apolyvinylidene fluoride (PVDF) membrane, or a cellulose acetatemembrane. In some examples, the immunoassay may be in a Western blotassay format or a lateral flow assay format.

In some embodiments, the support member is a multi-well plate, such asan ELISA plate. In some embodiments, the immunoassays described hereincan be carried out on high throughput platforms. In some embodiments,multi-well plates, e.g., 24-, 48-, 96-, 384- or greater well plates, maybe used for high throughput detection assays. In the kit or detectingdevice, one or more of the binding agents may be immobilized on asupport member, which can be a membrane, a bead, a slide, or amulti-well plate. Selection of an appropriate support member for theimmunoassay will depend on various factor such as the number of samplesand method of detecting the signal released from label conjugated to thesecond agent. The kit can also comprise one or more buffers as describedherein but not limited to a coating buffer, a blocking buffer, a washbuffer, and/or a stopping buffer.

In some embodiments, the kit can comprise instructions for use inaccordance with any of the methods described herein. The instructionsrelating to the use of the kit generally include information as to theamount of each component and suitable conditions for performing theassay methods described herein. The components in the kits may be inunit doses, bulk packages (e.g., multi-dose packages), or sub-unitdoses. Instructions supplied in the kits of the present disclosure aretypically written instructions on a label or package insert (e.g., apaper sheet included in the kit), but machine-readable instructions(e.g., instructions carried on a magnetic or optical storage disk) arealso acceptable. The label or package insert indicates that the kit isused for evaluating the level of immune system activation, selecting atreatment, and/or diagnostic purposes. Instructions may be provided forpracticing any of the methods described herein.

The kits of this present disclosure are in suitable packaging. Suitablepackaging includes, but is not limited to, vials, bottles, jars,flexible packaging (e.g., sealed Mylar or plastic bags), and the like.Kits may optionally provide additional components such as interpretiveinformation, such as a control and/or standard or reference sample.Normally, the kit comprises a container and a label or package insert(s)on or associated with the container. In some embodiments, the presentdisclosure provides articles of manufacture comprising contents of thekits described above. Table 1 below provides sequence identifier numbers(SEQ ID NOs) used in the compositions of the experiments disclosedherein. The closest bacterial species to the indicated strain ispresented by genus-species. The 16S rDNA sequence associated with eachgenus species identified as the closest related genus species is alsoprovided. The percent alignment presents the percent identity betweenthe sequence of the indicated strain with the sequence from the closestgenus species and the length of the alignment. The GenBank AccessionNumber of the closest related species is provided in the last column.

TABLE 1 Strains and species with highest homology NCBI SEQ ID ofaccession # NCBI 16S Strain # SEQ ID NO Strain ID Species with highesthomology of 16S locus locus 1 1 2G5 Phascolarctobacterium faeciumLN998073 27 2 2 1A6 Fusobacterium ulcerans KR822463 28 3 3 1B11Bacteroides dorei CP011531 29 4 4 2G1 Bacteroides uniformis NR112945 305 5 2B1 Subdoligranulum sp. KM098109 31 6 6 2A6 Paraprevotellaxylaniphila NR113078 32 7 7 2F11 Parabacteroides johnsonii NR041464 33 88 1E7 Alistipes sp. LT223566 34 9 9 1H9 Parabacteroides gordoniiNR112835 35 10 10 1C1 Eubacterum limosum NR113248 36 11 11 2G9Parabacteroides distasonis NR041342 37 12 12 2B7 Bacteroidescellulosilyticus NR112933 38 13 13 2C1 Bacteroides clarus NR112893 39 1414 1B4 Anaerostipes caccae HE974918 40 15 15 2A3 Bacteroides salyersiaeNR043016 41 16 16 2A12 Bacteroides fragilis AB618791 42 17 17 1A2Bacteroides uniformis AB215083 43 18 18 2B11 Bacteroides eggerthiiNR112935 44 19 19 2D2 Clostridium sp. AB249652 45 20 20 2E8Parabacteroides goldsteinii NR113076 46 21 21 1H8 Bacteroides sp.NR112944 47 22 22 3F2 Lachnospiraceae bacterium HGA0140 JX519760 48 2323 1G1 Hungatella hathewayi AJ311620 49 24 24 1E6 Clostridium lavalenseEF564278 50 25 25 1F3 Ruminococcus sp. KT156811 51 26 26 1A1 Clostridiuminnocuum HM008265 52

The nucleic acid sequences of the 16S rDNA, or portion thereof, for thebacterial strains described herein are provided below:

strain 1 2G5_Phascolarctobacterium faecium_LN998073 SEQ ID NO: 1GACGAACGCTGGCGGCGTGCCTAACACATGCAAGTCGAACGGAGAATTTTATTTCGGTAGAATTCTTAGTGGCGAACGGGTGAGTAACGCGTAGGCAACCTACCCTTTAGACGGGGACAACATTCCGAAAGGAGTGCTAATACCGGATGTGATCATCTTGCCGCATGGCAGGATGAAGAAAGATGGCCTCTACAAGTAAGCTATCGCTAAAGGATGGGCCTGCGTCTGATTAGCTAGTTGGTAGTGTAACGGACTACCAAGGCGATGATCAGTAGCCGGTCTGAGAGGATGAACGGCCACATTGGGACTGAGACACGGCCCAAACTCCTACGGGAGGCAGCAGTGGGGAATCTTCCGCAATGGACGAAAGTCTGACGGAGCAACGCCGCGTGAGTGATGAAGGATTTCGGTCTGTAAAGCTCTGTTGTTTATGACGAACGTGCAGTGTGTGAACAATGCATTGCAATGACGGTAGTAAACGAGGAAGCCACGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGTGGCGAGCGTTGTCCGGAATTATTGGGCGTAAAGAGCATGTAGGCGGCTTAATAAGTCGAGCGTGAAAATGCGGGGCTCAACCCCGTATGGCGCTGGAAACTGTTAGGCTTGAGTGCAGGAGAGGAAAGGGGAATTCCCAGTGTAGCGGTGAAATGCGTAGATATTGGGAGGAACACCAGTGGCGAAGGCGCCTTTCTGGACTGTGTCTGACGCTGAGATGCGAAAGCCAGGGTAGCGAACGGGATTAGATACCCCGGTAGTCCTGGCCGTAAACGATGGGTACTAGGTGTAGGAGGTATCGACCCCTTCTGTGCCGGAGTTAACGCAATAAGTACCCCGCCTGGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGTGGAGTATGTGGTTTAATTCGACGCAACGCGAAGAACCTTACCAAGGCTTGACATTGATTGAACGCTCTAGAGATAGAGATTTCCCTTCGGGGACAAGAAAACAGGTGGTGCATGGCTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCCTATCCTATGTTACCAGCAAGTAAAGTTGGGGACTCATGGGAGACTGCCAGGGACAACCTGGAGGAAGGCGGGGATGACGTCAAGTCATCATGCCCCTTATGTCTTGGGCTACACACGTACTACAATGGTCGGAAACAGAGGGAAGCGAAGCCGCGAGGCAGAGCAAACCCCAGAAACCCGATCTCAGTTCGGATCGCAGGCTGCAACCCGCCTGCGTGAAGTCGGAATCGCTAGTAATCGCAGGTCAGCATACTGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCACACCACGAAAGTTGGTAACACCCGAAGCCGGTGAGGTAACCTAstrain 2 1A6_ Fusobacterium ulcerans_KR822463 SEQ ID NO: 2GATGAACGCTGACAGAATGCTTAACACATGCAAGTCTACTTGATCCTTCGGGTGAAGGTGGCGGACGGGTGAGTAACGCGTAAAGAACTTGCCTTACAGACTGGGACAACATTTGGAAACGAATGCTAATACCGGATATTATGATTGGGTCGCATGATCTGATTATGAAAGCTATATGCGCTGTGAGAGAGCTTTGCGTCCCATTAGTTAGTTGGTGAGGTAACGGCTCACCAAGACGATGATGGGTAGCCGGCCTGAGAGGGTGAACGGCCACAAGGGGACTGAGACACGGCCCTTACTCCTACGGGAGGCAGCAGTGGGGAATATTGGACAATGGACCAAAAGTCTGATCCAGCAATTCTGTGTGCACGAAGAAGTTTTTCGGAATGTAAAGTGCTTTCAGTTGGGAAGAAGTCAGTGACGGTACCAACAGAAGAAGCGACGGCTAAATACGTGCCAGCAGCCGCGGTAATACGTATGTCGCAAGCGTTATCCGGATTTATTGGGCGTAAAGCGCGTCTAGGCGGCTTAGTAAGTCTGATGTGAAAATGCGGGGCTCAACCCCGTATTGCGTTGGAAACTGCTAAACTAGAGTACTGGAGAGGTAGGCGGAACTACAAGTGTAGAGGTGAAATTCGTAGATATTTGTAGGAATGCCGATGGGGAAGCCAGCCTACTGGACAGATACTGACGCTAAAGCGCGAAAGCGTGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGATTACTAGGTGTTGGGGGTCGAACCTCAGCGCCCAAGCTAACGCGATAAGTAATCCGCCTGGGGAGTACGTACGCAAGTATGAAACTCAAAGGAATTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGACGCAACGCGAGGAACCTTACCAGCGTTTGACATCCCAAGAAGTTAACAGAGATGTTTTCGTGCCTCTTCGGAGGAACTTGGTGACAGGTGGTGCATGGCTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCCTTTCGTATGTTACCATCATTAAGTTGGGGACTCATGCGAGACTGCCTGCGATGAGCAGGAGGAAGGTGGGGATGACGTCAAGTCATCATGCCCCTTATACGCTGGGCTACACACGTGCTACAATGGGTAGTACAGAGAGCTGCAAACCTGCGAGGGTAAGCTAATCTCATAAAACTATTCTTAGTTCGGATTGTACTCTGCAACTCGAGTACATGAAGTTGGAATCGCTAGTAATCGCAAATCAGCTATGTTGCGGTGAATACGTTCTCGGGTCTTGTACACACCGCCCGTCACACCACGAGAGTTGGTTGCACCTGAAGTAACAGGCCTAACCGTAAstrain 3 1B11_Bacteroides dorei_CP011531 SEQ ID NO: 3AGTTTGNNNTATGGCTCAGGATGAACGCTAGCTACAGGCTTAACACATGCAAGTCGAGGGGCAGCATGGTCTTAGCTTGCTAAGGCTGATGGCGACCGGCGCACGGGTGAGTAACACGTATCCAACCTGCCGTCTACTCTTGGCCAGCCTTCTGAAAGGAAGATTAATCCAGGATGGGATCATGAGTTCACATGTCCGCATGATTAAAGGTATTTTCCGGTAGACGATGGGGATGCGTTCCATTAGATAGTAGGCGGGGTAACGGCCCACCTAGTCAACGATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGGCGATGGCCTGAACCAGCCAAGTAGCGTGAAGGATGACTGCCCTATGGGTTGTAAACTTCTTTTATAAAGGAATAAAGTCGGGTATGCATACCCGTTTGCATGTACTTTATGAATAAGGATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGAGCGTAGATGGATGTTTAAGTCAGTTGTGAAAGTTTGCGGCTCAACCGTAAAATTGCAGTTGATACTGGATGTCTTGAGTGCAGTTGAGGCAGGCGGAATTCGTGGTGTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAGCCTGCTAAGCTGCAACTGACATTGAGGCTCGAAAGTGTGGGTATCAAACAGGATTAGATACCCTGGTAGTCCACACGGTAAACGATGAATACTCGCTGTTTGCGATATACGGCAAGCGGCCAAGCGAAAGCGTTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACCTTACCCGGGCTTAAATTGCACTCGAATGATCCGGAAACGGTTCAGCTAGCAATAGCGAGTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTGTTGTCAGTTACTAACAGGTGATGCTGAGGACTCTGACAAGACTGCCATCGTAAGATGTGAGGAAGGTGGGGATGACGTCAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGGGGGTACAGAGGGCCGCTACCACGCGAGTGGATGCCAATCCCTAAAACCCCTCTCAGTTCGGACTGGAGTCTGCAACCCGACTCCACGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCACGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGGGAGCCGGGGGTACCTGAAGTGCGTAACCGCGAGGATstrain 4 2G1_Bacteroides uniformis_NR_112945 SEQ ID NO: 4GATGAACGCTAGCTACAGGCTTAACACATGCAAGTCGAGGGGCAGCATGAACTTAGCTTGCTAAGTTTGATGGCGACCGGCGCACGGGTGAGTAACACGTATCCAACCTGCCGATGACTCGGGGATAGCCTTTCGAAAGAAAGATTAATACCCGATGGCATAGTTCTTCCGCATGGTAGAACTATTAAAGAATTTCGGTCATCGATGGGGATGCGTTCCATTAGGTTGTTGGCGGGGTAACGGCCCACCAAGCCTTCGATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGACGAGAGTCTGAACCAGCCAAGTAGCGTGAAGGATGACTGCCCTATGGGTTGTAAACTTCTTTTATACGGGAATAAAGTGAGGCACGTGTGCCTTTTTGTATGTACCGTATGAATAAGGATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGAGCGTAGGCGGACGCTTAAGTCAGTTGTGAAAGTTTGCGGCTCAACCGTAAAATTGCAGTTGATACTGGGTGTCTTGAGTACAGTAGAGGCAGGCGGAATTCGTGGTGTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAGCCTGCTGGACTGTAACTGACGCTGATGCTCGAAAGTGTGGGTATCAAACAGGATTAGATACCCTGGTAGTCCACACCAGTAAACGATGAATACTCGCTGTTTGCGATATACAGTAAGCGGCCAAGCGAAAGCGTTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACCTTACCCGGGCTTGAATTGCAACTGAATGATGTGGAGACATGTCAGCCGCAAGGCAGTTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTATCGATAGTTACCATCAGGTGATGCTGGGGACTCTGTCGAGACTGCCGTCGTAAGATGTGAGGAAGGTGGGGATGACGTCAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGGGGGTACAGAAGGCAGCTACACGGCGACGTGATGCTAATCCCGAAAGCCTCTCTCAGTTCGGATTGGAGTCTGCAACCCGACTCCATGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCACGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGAAAGCCGGGGGTACCTGAAGTGCGTAACCGCAAGGAGstrain 5 2B1_ Subdoligranulum sp. 4_3_54A2FAA_NZ-ACWW00000000SEQ ID NO: 5GACGAACGCTGGCGGCGCGCCTAACACATGCAAGTCGAACGGAGCTGTTTTCTCTGAAGTTTTCGGATGGAAGAGAGTTCAGCTTAGTGGCGAACGGGTGAGTAACACGTGAGCAACCTGCCTTTCAGTGGGGGACAACATTTGGAAACGAATGCTAATACCGCATAAGACCACAGTGTCGCATGGCACAGGGGTCAAAGGATTTATCCGCTGAAAGATGGGCTCGCGTCCGATTAGCTAGATGGTGAGGTAACGGCCCACCATGGCGACGATCGGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCTGATGCAGCGACGCCGCGTGGAGGAAGAAGGTCTTCGGATTGTAAACTCCTGTCCCAGGGGACGATAATGACGGTACCCTGGGAGGAAGCACCGGCTAACTACGTGCCAGCAGCCGCGGTAAAACGTAGGGTGCAAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGCAGGCGGATTGGCAAGTTGGGAGTGAAATCTATGGGCTCAACCCATAAATTGCTTTCAAAACTGTCAGTCTTGAGTGGTGTAGAGGTAGGCGGAATTCCCGGTGTAGCGGTGGAATGCGTAGATATCGGGAGGAACACCAGTGGCGAAGGCGGCCTACTGGGCACTAACTGACGCTGAGGCTCGAAAGCATGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCATGCCGTAAACGATGATTACTAGGTGTGGGAGGATTGACCCCTTCCGTGCCGCAGTTAACACAATAAGTAATCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACATCGGATGCATACCTAAGAGATTAGGGAAGTCCTTCGGGACATCCAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATCGTTAGTTACTACGCAAGAGGACTCTAGCGAGACTGCCGTTGACAAAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCTTTATGACCTGGGCTACACACGTACTACAATGGCTATTAACAGAGAGAAGCGATACCGCGAGGTGGAGCAAACCTCACAAAAATAGTCTCAGTTCGGATCGCAGGCTGCAACCCGCCTGCGTGAAGCCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCACACCATGAGAGCCGGGGGGACCCGAAGTCGGTAGTCTAACCGC strain 6 2A6_Paraprevotella xylaniphila_AB 331897SEQ ID NO: 6GATGAACGCTAGCTACAGGCTTAACACATGCAAGTCGAGGGGCAGCATGAACTTAGCTTGCTAAGTTTGATGGCGACCGGCGCACGGGTGAGTAACGCGTATCCAACCTGCCCTTTACCCGGGGATAGCCTTCTGAAAAGGAAGTTTAATACCCGATGAATTCGTTTAGTCGCATGGCTNGATGAATAAAGATTAATTGGTAAAGGATGGGGATGCGTCCCATTAGCTTGTTGGCGGGGTAACGGCCCACCAAGGCGACGATGGGTAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGGCGCGAGCCTGAACCAGCCAAGTAGCGTGGAGGACGACGGCCCTACGGGTTGTAAACTCCTTTTATAAGGGGATAAAGTTGGCCATGTATGGCCATTTGCAGGTACCTTATGAATAAGCATCGGCTAATTCCGTGCCAGCAGCCGCGGTAATACGGAAGATGCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGAGCGTAGGCGGGCTGTCAAGTCAGCGGTCAAATGGCGCGGCTCAACCGCGTTCCGCCGTTGAAACTGGCAGCCTTGAGTATGCACAGGGTACATGGAATTCGTGGTGTAGCGGTGAAATGCTTAGATATCACGAGGAACTCCGATCGCGCAGGCATTGTACCGGGGCATTACTGACGCTGAGGCTCGAAGGTGCGGGTATCAAACAGGATTAGATACCCTGGTAGTCCGCACAGTAAACGATGAATGCCCGCTGTCGGCGACATAGTGTCGGCGGCCAAGCGAAAGCGTTAAGCATTCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACCTTACCCGGGCTTGAATCGCAGGTGCATGGGCCGGAGACGGCCCTTTCCTTCGGGACTCCTGCGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCCCCTCCCCAGTTGCCACCGGGTAATGCCGGGCACTTTGGGGACACTGCCACCGCAAGGTGCGAGGAAGGTGGGGATGACGTCAAATCAGCACGGCCCTTACGTCCGGGGCGACACACGTGTTACAATGGGGGGTACAGAGGGCCGCTGCCCGGTGACGGTTGGCCAATCCCTAAAACCCCTCTCAGTTCGGACTGGAGTCTGCAACCCGACTCCACGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGAAAGCCGGGGGTGCCTGAAGTCCGTNNCCGCGAstrain 7 2F11_Parabacteroides johnsonii_AB261128 SEQ ID NO: 7GATGAACGCTAGCGACAGGCTTAACACATGCAAGTCGAGGGGCAGCATGGTAAGTAGCAATACTTATTGATGGCGACCGGCGCACGGGTGAGTAACGCGTATGCAACTTACCTATCAGAGGGGGATAGCCCGGCGAAAGTCGGATTAATACTCCATAAAACAGGGGTTCCGCATGGGACTATTTGTTAAAGATTCATCGCTGATAGATAGGCATGCGTTCCATTAGGCAGTTGGCGGGGTAACGGCCCACCAAACCGACGATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGTACTGAGACACGGACCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGCCGAGAGGCTGAACCAGCCAAGTCGCGTGAAGGATGAAGGATCTATGGTTTGTAAACTTCTTTTATAGGGGAATAAAGTGTGGGACGTGTTCCATTTTGTATGTACCCTATGAATAAGCATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATGCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGTGCGTAGGTGGTAATTTAAGTCAGCGGTGAAAGTTTGTGGCTCAACCATAAAATTGCCGTTGAAACTGGGTTACTTGAGTGTGTTTGAGGTAGGCGGAATGCGTGGTGTAGCGGTGAAATGCATAGATATCACGCAGAACTCCAATTGCGAAGGCAGCTTACTAAACCATAACTGACACTGAAGCACGAAAGCGTGGGTATCAAACAGGATTAGATACCCTGGTAGTCCACGCAGTAAACGATGATTACTAGGAGTTTGCGATACACAGTAAGCTCTACAGCGAAAGCGTTAAGTAATCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACCTTACCCGGGTTTGAACGTAGTCAGACCGACCTTGAAAGAGGTTTTCTAGCAATAGCTGATTACGAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTATCACTAGTTACTAACAGGTTAAGCTGAGGACTCTGGTGAGACTGCCAGCGTAAGCTGTGAGGAAGGTGGGGATGACGTCAAATCAGCACGGCCCTTACATCCGGGGCGACACACGTGTTACAATGGCATGGACAAAGGGCAGCTACCTGGCGACAGGATGCTAATCTCTAAACCATGTCTCAGTTCGGATCGGAGTCTGCAACTCGACTCCGTGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGGGAGCCGGGGGTACCTGAAGTCCGTAACCGCAAstrain 8 1E7_Alistipes sp. JC136_NZ-CAEG00000000 SEQ ID NO: 8GATGAACGCTAGCGGCAGGCCTAACACATGCAAGTCGAGGGGCAGCGGGATTGAAGCTTGCTTCAGTTGCCGGCGACCGGCGCACGGGTGCGTAACGCGTATGCAACCTACCCATAACAGGGGGATAACACTGAGAAATCGGTACTAATATCCCATAACATCAAGAGGGGCATCCCTTTTGGTTGAAAACTCCGGTGGTTATGGATGGGCATGCGTTGTATTAGCTAGTTGGTGAGGTAACGGCTCACCAAGGCGACGATACATAGGGGGACTGAGAGGTTAACCCCCCACATTGGTACTGAGACACGGACCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGACGCAAGTCTGAACCAGCCATGCCGCGTGCAGGATGACGGCTCTATGAGTTGTAAACTGCTTTTGTACGAGGGTAAACCCGGATACGTGTATCCGGCTGAAAGTATCGTACGAATAAGGATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATTCAAGCGTTATCCGGATTTATTGGGTTTAAAGGGTGCGTAGGCGGTTTGATAAGTTAGAGGTGAAATACCGGTGCTTAACACCGGAACTGCCTCTAATACTGTTGAGCTAGAGAGTAGTTGCGGTAGGCGGAATGTATGGTGTAGCGGTGAAATGCTTAGAGATCATACAGAACACCGATTGCNGAAGGCAGCTTACCAAACTATATCTGACGTTNGAGGCACGAAAGCGTGGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCAGTAAACGATGATAACTCGCTGTCGGCGATACACAGTCGGTGGCTAAGCGAAAGCGATAAGTTATCCACCTGGGGAGTACGTTCGCAAGAATGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACCTTACCCGGGCTTGAAAGTTACTGACGATTCTGGAAACAGGATTTCCCTTCGGGGCAGGAAACTAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGGTTAAGTCCCATAACGAGCGCAACCCCTACCGTTAGTTGCCATCAGGTCAAGCTGGGCACTCTGGCGGGACTGCCGGTGTAAGCCGAGAGGAAGGTGGGGATGACGTCAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGTAGGTACAGAGGGCAGCTACCCAGTGATGGGATGCGAATCTCGAAAGCCTATCTCAGTTCGGATTGGAGGCTGAAACCCGCCTCCATGAAGTTGGATTCGCTAGTAATCGCGCATCAGCCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGGAAGCTGGGGGTGCCTGAAGTTCGTGAC strain 9 1H9_Parabacteroides gordonii_AB470343SEQ ID NO: 9GATGAACGCTAGCGACAGGCTTAACACATGCAAGTCGAGGGGCAGCAGGAAGTAGCAATACTTTGCTGGCGACCGGCGCACGGGTGAGTAACGCGTATGCAACCTACCTATCAGAGGGGGATAACCCGGCGAAAGTCGGACTAATACCGCATAAAACAGGGGTCCCGCATGGGAATATTTGTTAAAGATTTATTGCTGATAGATGGGCATGCGTTCCATTAGATAGTTGGTGAGGTAACGGCTCACCAAGTCTTCGATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACACTGGTACTGAGACACGGACCAGACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGGCGAGAGCCTGAACCAGCCAAGTCGCGTGAAGGATGAAGGATCTATGGTTCGTAAACTTCTTTTATAGGGGAATAAAGTGCAGGACGTGTCCTGTTTTGTATGTACCCTATGAATAAGGATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGTGCGTAGGTGGCTTTTTAAGTCAGCGGTGAAAGTTTGTGGCTCAACCATAAAATTGCCGTTGAAACTGGAGGGCTTGAGTATATTTGAGGTAGGCGGAATGCGTGGTGTAGCGGTGAAATGCATAGATATCACGCAGAACTCCAATTGCGAAGGCAGCTTACTAAACTATAACTGACACTGAAGCACGAAAGCGTGGGGATCAAACAGGATTAGATACCCTGGTAGTCCACGCAGTAAACGATGATTACTAGGAGTTTGCGATACACAGTAAGCTCTACAGCGAAAGCGTTAAGTAATCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACCTTACCCGGGTTTGAACGTAAGTTGACCGGAGTGGAAACACTCTTTCTAGCAATAGCAATTTACGAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTATCTTTAGTTACTAACAGGTCGAGCTGAGGACTCTAAAGAGACTGCCAGCGTAAGCTGTGAGGAAGGTGGGGATGACGTCAAATCAGCACGGCCCTTACATCCGGGGCGACACACGTGTTACAATGGTGGGGACAAAGGGCAGCTACCTGGCGACAGGATGCTAATCTCCAAACCCCATCTCAGTTCGGATCGAAGTCTGCAACCCGACTTCGTGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGGGAGTTGGGGGTACCTAAAGTCCGTNACCGCAAG strain 10 1C1_Eubacterium limosum_AB595134SEQ ID NO: 10GACGAACGCTGGCGGTATGCTTAACACATGCAAGTCGAACGAGAAGGTTTTGATGGATCCTTCGGGTGACATTAGAACTGGAAAGTGGCGAACGGGTGAGTAACGCGTGGGTAACCTGCCCTATGGAAAGGAATAGCCTCGGGAAACTGGGAGTAAAGCCTTATATTATGGTTTTGTCGCATGGCAAGATCATGAAAACTCCGGTGCCATAGGATGGACCCGCGTCCCATTAGCTAGTTGGTGAGATAACAGCCCACCAAGGCGACGATGGGTAACCGGTCTGAGAGGGCGAACGGTCACACTGGAACTGAGACACGGTCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCGCAATGGGGGCAACCCTGACGCAGCAATACCGCGTGAGTGAAGAAGGTTTTCGGATCGTAAAGCTCTGTTATTGGGGAAGAAGAATGACGGTACCCAATGAGGAAGTCCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGGACAAGCGTTGTCCGGAATGACTGGGCGTAAAGGGCGCGTAGGCGGTCTATTAAGTCTGATGTGAAAGGTACCGGCTCAACCGGTGAAGTGCATTGGAAACTGGTAGACTTGAGTATTGGAGAGGCAAGTGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCTTGCTGGACAAATACTGACGCTGAGGTGCGAAAGCGTGGGGAGCGAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGAATGCTAGGTGTTGGGGAAACTCAGTGCCGCAGTTAACACAATAAGCATTCCGCCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACGGGGACCCGCACAAGCAGCGGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACATCCTCTGACGAGCCTAGAGATAGGAAGTTTCCTTCGGGAACAGAGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCCTGCCTTTAGTTGCCAGCATTAAGTTGGGCACTCTAGAGGGACTGCCGTAGACAATACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACACGTGCTACAATGGTCTGAACAGAGGGCCGCGAAGCCGCGAGGTGAAGCAAATCCCTTAAAACAGATCCCAGTTCGGATTGCAGGCTGCAACTCGCCTGCATGAAGTTGGAGTTGCTAGTAATCGCGGATCAGAATGCCGCGGTGAATGCGTTCCCGGGTCTTGTACACACCGCCCGTCACACCACGAGAGTTGGCAACACCCGAAGCCTGTGAGAGAACCGTAAGGACTCAGCAGTstrain 11 2G9_Parabacteroides distasonis_HE974920 SEQ ID NO: 11GATGAACGCTAGCGACAGGCTTAACACATGCAAGTCGAGGGGCAGCACAGGTAGCAATACCGGGTGGCGACCGGCGCACGGGTGAGTAACGCGTATGCAACTTGCCTATCAGAGGGGGATAACCCGGCGAAAGTCGGACTAATACCGCATGAAGCAGGGGCCCCGCATGGGGATATTTGCTAAAGATTCATCGCTGATAGATAGGCATGCGTTCCATTAGGCAGTTGGCGGGGTAACGGCCCACCAAACCGACGATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGTACTGAGACACGGACCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGCCGAGAGGCTGAACCAGCCAAGTCGCGTGAGGGATGAAGGTTCTATGGATCGTAAACCTCTTTTATAAGGGAATAAAGTGCGGGACGTGTCCCGTTTTGTATGTACCTTATGAATAAGGATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGTGCGTAGGCGGCCTTTTAAGTCAGCGGTGAAAGTCTGTGGCTCAACCATAGAATTGCCGTTGAAACTGGGGGGCTTGAGTATGTTTGAGGCAGGCGGAATGCGTGGTGTAGCGGTGAAATGCATAGATATCACGCAGAACCCCGATTGCGAAGGCAGCCTGCCAAGCCATTACTGACGCTGATGCACGAAAGCGTGGGGATCAAACAGGATTAGATACCCTGGTAGTCCACGCAGTAAACGATGATCACTAGCTGTTTGCGATACACTGTAAGCGGCACAGCGAAAGCGTTAAGTGATCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACCTTACCCGGGTTTGAACGCATTCGGACCGAGGTGGAAACACCTTTTCTAGCAATAGCCGTTTGCGAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTGCCACTAGTTACTAACAGGTAAAGCTGAGGACTCTGGTGGGACTGCCAGCGTAAGCTGCGAGGAAGGCGGGGATGACGTCAAATCAGCACGGCCCTTACATCCGGGGCGACACACGTGTTACAATGGCGTGGACAAAGGGAAGCCACCTGGCGACAGGGAGCGAATCCCCAAACCACGTCTCAGTTCGGATCGGAGTCTGCAACCCGACTCCGTGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGGGAGCCNGGGGTACCTGAAGTCCGTAACCGCGAstrain 12 2B7_Bacteroides cellulosilyticus_NR_112933 SEQ ID NO: 12GATGAACGCTAGCTACAGGCTTAACACATGCAAGTCGAGGGGCAGCATGACCTAGCAATAGGTTGATGGCGACCGGCGCACGGGTGAGTAACACGTATCCAACCTACCGGTTATTCCGGGATAGCCTTTCGAAAGAAAGATTAATACCGGATAGTATAACGAGAAGGCATCTTTTTGTTATTAAAGAATTTCGATAACCGATGGGGATGCGTTCCATTAGTTTGTTGGCGGGGTAACGGCCCACCAAGACATCGATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGACGAGAGTCTGAACCAGCCAAGTAGCGTGAAGGATGACTGCCCTATGGGTTGTAAACTTCTTTTATATGGGAATAAAGTGAGCCACGTGTGGCTTTTTGTATGTACCATACGAATAAGGATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGAGCGTAGGCGGACTATTAAGTCAGCTGTGAAAGTTTGCGGCTCAACCGTAAAATTGCAGTTGATACTGGTCGTCTTGAGTGCAGTAGAGGTAGGCGGAATTCGTGGTGTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAGCTTACTGGACTGTAACTGACGCTGATGCTCGAAAGTGTGGGTATCAAACAGGATTAGATACCCTGGTAGTCCACACAGTAAACGATGAATACTCGCTGTTTGCGATATACAGCAAGCGGCCAAGCGAAAGCATTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACCTTACCCGGGCTTAAATTGCATCTGAATAATTTGGAAACAGATTAGCCGTAAGGCAGATGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTATCTTTAGTTACTAACAGGTCATGCTGAGGACTCTAGAGAGACTGCCGTCGTAAGATGTGAGGAAGGTGGGGATGACGTCAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGGGGGTACAGAAGGCAGCTACACAGCGATGTGATGCTAATCCCAAAAGCCTCTCTCAGTTCGGATTGGAGTCTGCAACCCGACTCCATGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCACGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGAAAGCCGGGGGTACCTGAAGTCCGTAAC strain 13 2C1_Bacteroides clarus_AB490801 SEQ ID NO: 13GATGAACGCTAGCTACAGGCTTAACACATGCAAGTCGAGGGGCAGCGGGGTTGAAGCTTGCTTCAACCGCCGGCGACCGGCGCACGGGTGAGTAACACGTATCCAACCTGCCGATAACTCCGGGATAGCCTTTCGAAAGAAAGATTAATACCGGATGGCATAGTTTTCCCGCATGGAATAACTATTAAAGAATTTCGGTTATCGATGGGGATGCGTTCCATTAGGCAGTTGGCGGGGTAACGGCCCACCAAACCGACGATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGACGAGAGTCTGAACCAGCCAAGTAGCGTGAAGGATGACTGCCCTATGGGTTGTAAACTTCTTTTATACGGGAATAAAGTTGGCCACGTGTGGTTTTTTGCATGTACCGTATGAATAAGGATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGAGCGTAGGCGGGGTATTAAGTCAGTTGTGAAAGTTTGCGGCTCAACCGTAAAATTGCAGTTGATACTGGTATCCTTGAGTGCAGCAGAGGTGGGCGGAATTCGTGGTGTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAGCTCACTGGAGTGTAACTGACGCTGATGCTCGAAAGTGTGGGTATCAAACAGGATTAGATACCCTGGTAGTCCACACAGTAAACGATGAATACTCGCTGTTGGCGATACAATGTCAGCGGCCAAGCGAAAGCATTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACCTTACCCGGGCTTGAATTGCAACTGACTGAGCTGGAAACAGTTCTTTCTTCGGACAGTTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTATCTATAGTTACCATCAGGTCATGCTGGGGACTCTATGGAGACTGCCGTCGTAAGATGTGAGGAAGGTGGGGATGACGTCAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGGGGGTACAGAAGGCAGCTACACGGCGACGTGATGCTAATCCCAAAAACCTCTCTCAGTTCGGATTGGAGTCTGCAACCCGACTCCATGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCACGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGAAAGCCGGGGGTACCTGAAGTACGTAACCGCAAstrain 14 1B4_Anaerostipes sp. 3_2_56FAA_NZ-ACWB00000000 SEQ ID NO: 14GATGAACGCTGGCGGCGTGCTTAACACATGCAAGTCGAACGAAGCATTTAGGATTGAAGTTTTCGGATGGATTTCCTATATGACTGAGTGGCGGACGGGTGAGTAACGCGTGGGGAACCTGCCCTATACAGGGGGATAACAGCTGGAAACGGCTGCTAATACCGCATAAGCGCACAGAATCGCATGATTCAGTGTGAAAAGCCCTGGCAGTATAGGATGGTCCCGCGTCTGATTAGCTGGTTGGTGAGGTAACGGCTCACCAAGGCGACGATCAGTAGCCGGCTTGAGAGAGTGAACGGCCACATTGGGACTGAGACACGGCCCAAACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCTGATGCAGCGACGCCGCGTGAGTGAAGAAGTATTTCGGTATGTAAAGCTCTATCAGCAGGGAAGAAAACAGACGGTACCTGACTAAGAAGCCCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGGGCAAGCGTTATCCGGAATTACTGGGTGTAAAGGGTGCGTAGGTGGCATGGTAAGTCAGAAGTGAAAGCCCGGGGCTTAACCCCGGGACTGCTTTTGAAACTGTCATGCTGGAGTGCAGGAGAGGTAAGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCTTACTGGACTGTCACTGACACTGATGCACGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGAATACTAGGTGTCGGGGCCGTAGAGGCTTCGGTGCCGCAGCAAACGCAGTAAGTATTCCACCTGGGGAGTACGTTCGCAAGAATGAAACTCAAAGGANTTGACGGGGACCGCNNNAGCGGTGGAGCATGTGGTTAATTCGAAGCACGCGAAGstrain 15 2A3_Bacteroides salyersiae_AY608696 SEQ ID NO: 15GATGAACGCTAGCTACAGGCTTAACACATGCAAGTCGAGGGGCATCAGGGTGTAGCAATACACCGCTGGCGACCGGCGCACGGGTGAGTAACACGTATCCAACCTGCCCTTTACTCGGGGATAGCCTTTCGAAAGAAAGATTAATACCCGATGGTATAACATGACCTCCTGGTTTTGTTATTAAAGAATTTCGGTAGAGGATGGGGATGCGTTCCATTAGGCAGTTGGCGGGGTAACGGCCCACCAAACCTTCGATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGGCGAGAGCCTGAACCAGCCAAGTAGCGTGAAGGATGACCGCCCTATGGGTTGTAAACTTCTTTTATATGGGAATAAAGTCTGCCACGTGTGGCATTTTGTATGTACCATATGAATAAGGATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGAGCGTAGGTGGACATGTAAGTCAGTTGTGAAAGTTTGCGGCTCAACCGTAAAATTGCAGTTGAAACTGCGTGTCTTGAGTACAGTAGAGGTGGGCGGAATTCGTGGTGTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAGCTCACTGGACTGCAACTGACACTGATGCTCGAAAGTGTGGGTATCAAACAGGATTAGATACCCTGGTAGTCCACACAGTAAACGATGAATACTCGCTGTTTGCGATATACAGTAAGCGGCCAAGCGAAAGCATTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACCTTACCCGGGCTTAAATTGCAAATGAATATGCCGGAAACGGCATAGCCGCAAGGCATTTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTATCTTCAGTTACTAACAGGTCATGCTGAGGACTCTGGAGAGACTGCCGTCGTAAGATGTGAGGAAGGTGGGGATGACGTCAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGGGGGTACAGAAGGCCGCTACACAGCGATGTGATGCCAATCCCTAAAGCCCCTCTCAGTTCGGATCGAAGTCTGCAACCCGACTTCGTGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCACGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGGGAGCCGGGGGTACCTGAAGTACGTAAC strain 16 2A12_Bacteroides fragilis_CR626927SEQ ID NO: 16GATGAACGCTAGCTACAGGCTTAACACATGCAAGTCGAGGGGCATCAGGAAGAAAGCTTGCTTTCTTTGCTGGCGACCGGCGCACGGGTGAGTAACACGTATCCAACCTGCCCTTTACTCGGGGATAGCCTTTCGAAAGAAAGATTAATACCCGATAGCATAATGATTCCGCATGGTTTCATTATTAAAGGATTCCGGTAAAGGATGGGGATGCGTTCCATTAGGTTGTTGGTGAGGTAACGGCTCACCAAGCCTTCGATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGGCGCTAGCCTGAACCAGCCAAGTAGCGTGAAGGATGAAGGCTCTATGGGTCGTAAACTTCTTTTATATAAGAATAAAGTGCAGTATGTATACTGTTTTGTATGTATTATATGAATAAGGATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGAGCGTAGGTGGACTGGTAAGTCAGTTGTGAAAGTTTGCGGCTCAACCGTAAAATTGCAGTTGATACTGTCAGTCTTGAGTACAGTAGAGGTGGGCGGAATTCGTGGTGTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAGCTCACTGGACTGCAACTGACACTGATGCTCGAAAGTGTGGGTATCAAACAGGATTAGATACCCTGGTAGTCCACACAGTAAACGATGAATACTCGCTGTTTGCGATATACAGTAAGCGGCCAAGCGAAAGCATTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACCTTACCCGGGCTTAAATTGCAGTGGAATGATGTGGAAACATGTCAGTGAGCAATCACCGCTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTATCTTTAGTTACTAACAGGTTATGCTGAGGACTCTAGAGAGACTGCCGTCGTAAGATGTGAGGAAGGTGGGGATGACGTCAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGGGGGTACAGAAGGCAGCTAACGGGTGACCGTATGCTAATCCCAAAAGCCTCTCTCAGTTCGGATCGAAGTCTGCAACCCGACTTCGTGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCACGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGGGAGCCGGGGGTACCTGAAGTACGTAACCGCAA strain 17 1A2_Bacteroides uniformis_AB247141SEQ ID NO: 17GATGAACGCTAGCTACAGGCTTAACACATGCAAGTCGAGGGGCATCAGGAAGAAAGCTTGCTTTCTTTGCTGGCGACCGGCGCACGGGTGAGTAACACGTATCCAACCTGCCGATGACTCGGGGATAGCCTTTCGAAAGAAAGATTAATACCCGATGGTATATCTGAAAGGCATCTTTCAGCTATTAAAGAATTTCGGTCATTGATGGGGATGCGTTCCATTAGGTTGTTGGCGGGGTAACGGCCCACCAAGCCATCGATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGACGAGAGTCTGAACCAGCCAAGTAGCGTGAAGGATGACTGCCCTATGGGTTGTAAACTTCTTTTATACGGGAATAAAGTTAGGCACGTGTGCCTTTTTGTATGTACCGTATGAATAAGGATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGAGCGTAGGCGGATGCTTAAGTCAGTTGTGAAAGTTTGCGGCTCAACCGTAAAATTGCAGTTGATACTGGGTGTCTTGAGTACAGTAGAGGCAGGCGGAATTCGTGGTGTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAGCTTGCTGGACTGTAACTGACGCTGATGCTCGAAAGTGTGGGTATCAAACAGGATTAGATACCCTGGTAGTCCACACAGTAAACGATGAATACTCGCTGTTTGCGATATACAGTAAGCGGCCAAGCGAAAGCGTTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACCTTACCCGGGCTTAAATTGCAAATGAATGTTCTGGAAACAGATCAGCCGCAAGGCATTTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTATCGATAGTTACCATCAGGTTATGCTGGGGACTCTGTCGAGACTGCCGTCGTAAGATGTGAGGAAGGTGGGGATGACGTCAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGGGGGTACAGAAGGCAGCTACACGGCGACGTGATGCTAATCCCTAAAACCTCTCTCAGTTCGGATTGGAGTCTGCAACCCGACTCCATGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCACGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGAAAGCCGGGGGTACCTGAAGTGCGT strain 18 2B11_Bacteroides eggerthii_NR_112935SEQ ID NO: 18GATGAACGCTAGCTACAGGCTTAACACATGCAAGTCGAGGGGCAGCATGATTGAAGCTTGCTTCAATCGATGGCGACCGGCGCACGGGTGAGTAACACGTATCCAACCTGCCGATAACTCGGGGATAGCCTTTCGAAAGAAAGATTAATACCCGATAGCATAGTATTTCCGCATGGTTTCACTATTAAAGAATTTCGGTTATCGATGGGGATGCGTTCCNTTAGATAGTTGGCGGGGTAACGGCCCACCAAGTCAACGATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGACGAGAGTCTGAACCAGCCAAGTAGCGTGAAGGATGACTGCCCTATGGGTTGTAAACTTCTTTTATACGGGAATAAAGTGGAGTATGCATACTCCTTTGTATGTACCGTATGAATAAGGATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGAGCGTAGGCGGGTGCTTAAGTCAGTTGTGAAAGTTTGCGGCTCAACCGTAAAATTGCAGTTGATACTGGGCGCCTTGAGTGCAGCATAGGTAGGCGGAATTCGTGGTGTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAGCTTACTGGACTGTAACTGACGCTGATGCTCGAAAGTGTGGGTATCAAACAGGATTAGATACCCTGGTAGTCCACACAGTAAACGATGAATACTCGCTGTTGGCGATACACAGTCAGCGGCCAAGCGAAAGCATTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACCTTACCCGGGCTTAAATTGCAGCGGAATGTAGTGGAAACATTACAGCCTTCGGGCCGCTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTATCTATAGTTACTATCAGGTCATGCTGAGGACTCTATGGAGACTGCCGTCGTAAGATGTGAGGAAGGTGGGGATGACGTCAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGGGGGTACAGAAGGCAGCTACCTGGCGACAGGATGCTAATCCCTAAAACCTCTCTCAGTTCGGATTGGAGTCTGCAACCCGACTCCATGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCACGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGAAAGCCGGGGGTACCTGAAGTACGTAACCGCAAGGAGCstrain 19 2D2_Clostridium sp. TM-40_AB249652 SEQ ID NO: 19GATGAACGCTGGCGGCGTGCCTAATACATGCAAGTCGGACGCAATGCTTCGGCATTGAGTGGCGAACGGGTGAGTAATACATAAGCAACCTGCCCCTGTGAGGGGGATAACTGCTGGAAACGGCAGCTAAGACCGCATATGCATACATGACGCATGTCGAGTATGTTAAATATCCCACGGGATAGCACAGGGATGGGCTTATGACGCATTAGCTAGCTGGTGAGGTAGAGGCTCACCAGGGCGACGATGCGTAGCCGGCCTGAGAGGGTGGACGGCCACACTGGGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTAGGGAATTTTCGGCAATGGGCGAAAGCCTGACCGAGCAACGCCGCGTGAAGGAAGAAGTCATTCGTGATGTAAACTTCTGTTATAAAGGAAGAACGGCGCCTGTAGGGAATGACAGGCGAGTGACGGTACTTTATGAGGAAGCCACGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGTGGCGAGCGTTATCCGGAATCATTGGGCGTAAAGAGGGAGCAGGCGGCAGTGCAGGTCTGCGGTGAAAGCCCGAAGCTAAACTTCGGTAAGCCGTGGAAACCGCACAGCTAGAGAGCATCAGAGGATCGCGGAATTCCATGTGTAGCGGTGAAATGCGTAGATATATGGAGGAACACCAGTGGCGAAGGCGGCGGTCTGGGGTGCAGCTGACGCTCAGTCCCGAAAGCGTGGGGAGCAAATAGGATTAGATACCCTAGTAGTCCACGCCGTAAACGATGAGTGCTAAGTGTTGGGGGTCAGACCTCAGTGCTGCAGTTAACGCAATAAGCACTCCGCCTGAGTAGTACGTTCGCAAGAATGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACATGGAGATAAAGGCTCTGGAGACAGAGAGATAGGTATATCTCACACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCCTGTTGCCAGTTGCCAGCATTAGGTTGGGGACTCTGGCGAGACTGCCTCTGCAAGGAGGAGGAAGGCGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACACGTGCTACAATGGACGGATCAGAGGGAGGCGAAGCCGCGAGGTGGAGCGAAACCCAGAAACCCGTTCACAGTTCGGACTGCAGTCTGCAACTCGACTGCACGAAGCTGGAATCGCTAGTAATCGCGAATCAGCATGTCGCGGTGAATACGTTCTCGGGCCTTGTACACACCGCCCGTCACACCATGAGAGTTGGTAACACCCGAAGCCGGTGGCCCAACCGCAA strain 20 2E8_Parabacteroides goldsteinii_NR_113076SEQ ID NO: 20GATGAACGCTAGCGACAGGCTTAACACATGCAAGTCGAGGGGCAGCACGATGTAGCAATACATTGGTGGCGACCGGCGCACGGGTGAGTAACGCGTATGCAACCTACCTATCAGAGGGGAATAACCCGGCGAAAGTCGGACTAATACCGCATAAAACAGGGGTTCCACATGGAAATATTTGTTAAAGAATTATCGCTGATAGATGGGCATGCGTTCCATTAGATAGTTGGTGAGGTAACGGCTCACCAAGTCCACGATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACACTGGTACTGAGACACGGACCAGACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGGCGAGAGCCTGAACCAGCCAAGTCGCGTGAAGGATGAAGGATCTATGGTTTGTAAACTTCTTTTATATGGGAATAAAGTGAGGAACGTGTTCCTTTTTGTATGTACCATATGAATAAGCATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATGCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGTGCGTAGGTGGTTAATTAAGTCAGCGGTGAAAGTTTGTGGCTCAACCATAAAATTGCCGTTGAAACTGGTTGACTTGAGTATATTTGAGGTAGGCGGAATGCGTGGTGTAGCGGTGAAATGCATAGATATCACGCAGAACTCCGATTGCGAAGGCAGCTTACTAAACTATAACTGACACTGAAGCACGAAAGCGTGGGGATCAAACAGGATTAGATACCCTGGTAGTCCACGCAGTAAACGATGATTACTAGCTGTTTGCGATACACAGTAAGCGGCACAGCGAAAGCGTTAAGTAATCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACCTTACCCGGGTTTGAACGCATATTGACAGCTCTGGAAACAGAGTCTCTAGTAATAGCAATTTGCGAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTATCACTAGTTACTAACAGGTCATGCTGAGGACTCTAGTGAGACTGCCAGCGTAAGCTGTGAGGAAGGTGGGGATGACGTCAAATCAGCACGGCCCTTACATCCGGGGCGACACACGTGTTACAATGGTGGGGACAAAGGGCAGCTACCGTGTGAGCGGATGCAAATCTCCAAACCCCATCTCAGTTCGGATCGAAGTCTGCAACCCGACTTCGTGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGGGAGTTGGGGGTACCTAAAGTCCGTAACCGC strain 21 1H8_Bacteroides sp. AR29_AF139525SEQ ID NO: 21GATGAACGCTAGCTACAGGCTTAACACATGCAAGTCGAGGGGCAGCATTTCAGTTTGCTTGCAAACTGGAGATGGCGACCGGCGCACGGGTGAGTAACACGTATCCAACCTGCCGATAACTCGGGGATAGCCTTTCGAAAGAAAGATTAATACCCGATGGTATAATNAGACCGCATGGTCTTGTTATTAAAGAATTTCGGTTATCGATGGGGATGCGTTCCATTAGGCAGTTGGTGAGGTAACGGCTCACCAAACCTTCGATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGGCGCAGGCCTGAACCAGCCAAGTAGCGTGAAGGATGACTGCCCTATGGGTTGTAAACTTCTTTTATATGGGAATAAAGTTTTCCACGTGTGGAATTTTGTATGTACCATATGAATAAGGATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGAGCGTAGGTGGACAGTTAAGTCAGTTGTGAAAGTTTGCGGCTCAACCGTAAAATTGCAGTTGATACTGGCTGTCTTGAGTACAGTAGAGGTGGGCGGAATTCGTGGTGTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAGCTCACTGGACTGCAACTGACACTGATGCTCGAAAGTGTGGGTATCAAACAGGATTAGATACCCTGGTAGTCCACACAGTAAACGATGAATACTCGCTGTTTGCGATATACAGTAAGCGGCCAAGCGAAAGCATTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACCTTACCCGGGCTTAAATTGCATTTGAATATATTGGAAACAGTATAGCCGTAAGGCAAATGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTATCTTTAGTTACTAACAGGTCATGCTGAGGACTCTAGAGAGACTGCCGTCGTAAGATGTGA strain 22 >3F2-PREMIX.fasta SEQ ID NO: 22NNNNNNNNNTGCAGTCGAACGAAGCGATTTGAATGAAGTTTTCGGATGGATTTCAANTTGACTGAGTGGCGGACGGGTGAGTAACGCGTGGGTAACCTGCCCCATACAGGGGGATAACAGTTAGAAATGACTGCTAATACCGCATAAGACCACAGNNCCGCATGGTGCAGGGGTAAAAACTCCGGTGGTATGGGATGGACCCGCGTCTGATTAGCTTGTTGGCGGGGTAACGGCCCACCAAGGCGACGATCAGTAGCCGACCTGAGAGGGTGACCGGCCACATTGGGACTGAGACACGGCCCAAACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCTGATGCAGCGACGCCGCGTGAGTGATGAAGTATTTCGGTATGTAAAGCTCTATCAGCAGGGAAGAAAATGACGGTACCTGACTAAGAAGCCCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGAGCGTAGACGGCTGTGCAAGTCTGGAGTGAAAGCCCGGGGCTCAACCCCGGGACTGCTTTGGAAACTGTACGGCTGGAGTGCTGGAGAGGCAAGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCTTGCTGGACAGTAACTGACGTTGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGAATGCTAGGTGTCGGGGAGCAAAGCTCTTCGGTGCCGCCGCAAACGCAATAAGCATTCCACCTGGGGAGTACGTTCGCAAGAATGAAACTCAAAGGANTTGACGGGGACCGCACANNGGTGGAGCATGTGGTTATTCGAGCACGCGAAANCTTACCAGTCTTGNNNCCCCTGANGNNNNGTATGTCGCTNCTNNGNNNNGGN strain 23 >1G1_3-PREMIX.fasta SEQ ID NO: 23AGTTTGATTATGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAAGTCGAGCGAAGCGGTTTCAATGAAGTTTTCGGATGGATTTGAAATTGACTTAGCGGCGGACGGGTGAGTAACGCGTGGGTAACCTGCCTTACACTGGGGGATAACAGTTAGAAATGACTGCTAATACCGCATAAGCGCACAGGGCCGCATGGTCCGGTGTGAAAAACTCCGGTGGTGTAAGATGGACCCGCGTCTGATTAGGTAGTTGGCGGGGTAACGGCCCACCAAGCCGACGATCAGTAGCCGACCTGAGAGGGTGACCGGCCACATTGGGACTGAGACACGGCCCAAACTCCTACGGGAGGCAGCAGTGGGGAATATTGGACAATGGGCGAAAGCCTGATCCAGCGACGCCGCGTGAGTGAAGAAGTATTTCGGTATGTAAAGCTCTATCAGCAGGGAAGAAAATGACGGTACCTGACTAAGAAGCCCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGAGCGTAGACGGTTTAGCAAGTCTGAAGTGAAAGCCCGGGGCTCAACCCCGGTACTGCTTTGGAAACTGTTAGACTTGAGTGCAGGAGAGGTAAGTGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCTTACTGGACTGTAACTGACGTTGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGAATACTAGGTGTCGGGGGGCAAAGCCCTTCGGTGCCGCCGCAAACGCAATAAGTATTCCACCTGGGGAGTACGTTCGCAAGAATGAAACTCAAAGGAATTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAAGTCTTGACATCCCACTGAAAACACTTTAACCGGTGTCCCTCTTCGGAGCAGTGGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATCCTTAGTAGCCAGCGAGTAGAGTCGGGCACTCTGGGGAGACTGCCAGGGATAACCTGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGATTTGGGCTACACACGTGCTACAATGGCGTAAACAAAGGGAGGCAAAGGAGCGATCTGGAGCAAACCCCAAAAATAACGTCTCAGTTCGGATTGCAGGCTGCAACTCGCCTGCATGAAGCTGGAATCGCTAGTAATCGCGAATCAGAATGTCGCGGTGAATACGTTCCCGGGTCTTGTACACACCGCCCGTCACACCATGGGAGTTGGTAACGCCCGAAGTCAGTGACCCAACCGCAAGGAGGNAGCTGCCGAANNNNNNNstrain 24 >1E6_27Fmod-PREMIX_Length_957 SEQ ID NO: 24AGTTTGNNNNNGCTCAGGATGAACGCTGGCGGCGTGCCTAACACATGCAAGTCGAACGAAGCATTTCAGATGAAGTTTTCGGATGGATTCTGAGATGACTGAGTGGCGGACGGGTGAGTAACACGTGGATAACCTGCCTCACACTGGGGGACAACAGTTAGAAATGACTGCTAATACCGCATAAGCGCACAGTACCGCATGGTACAGTGTGAAAAACTCCGGTGGTGTGAGATGGATCCGCGTCTGATTAGCCAGTTGGCGGGGTAACGGCCCACCAAAGCGACGATCAGTAGCCGACCTGAGAGGGTGACCGGCCACATTGGGACTGAGACACGGCCCAAACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGCGAAAGCCTGATGCAGCGACGCCGCGTGAGTGAAGAAGTATTTCGGTATGTAAAGCTCTATCAGCAGGGAAGATAATGACGGTACCTGACTAAGAAGCCCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGAGCGTAGACGGCATGGCAAGTCTGAAGTGAAAACCCAGGGCTCAACCCTGGGACTGCTTTGGAAACTGTCAAGCTAGAGTGCAGGAGAGGTAAGTGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCTTACTGGACTGTAACTGACGTTGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGAGTGCTAGGTGTTGGGGGGCAAAGCCCTTCGGTGCCGTCGCAAACGCAATAAGCACTCCACCTGGGGAGTACGTTCGCAAGAATGAAACTCAAAGGAATTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAAGTCTTGACATCCTCTTGACCGGCGTGTAACGGCGCCTTTCCTTCGGGACAAGAGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATCCTTAGTAGCCAGCATTAAGATGGGCACTCTAGGGAGACTGCCAGGGACAACCTGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGATTTGGGCTACACACGTGCTACAATGGCGTAAACAAAGGGAAGCGACCCTGCGAAGGTGAGCAAATCTCAAAAATAACGTCCCAGTTCGGACTGTAGTCTGCAACCCGACTACACGAAGCNNGAATCGCTAGTAATCGCGAATCAGAATGTCGCGGTGAATACGNTCCCGGGTCTTGTACACACCGCCCGTCACACCATGGGAGTCAGCAACGNCCGAAGTCAGTGACCCAACCGAAAGGAGGGAGNTGCNGAAGNNGNNNNNstrain 25 >1F3_27Fmod-PREMIX.fasta SEQ ID NO: 25AGTTTGANNTTGGCTCAGGATGAACGCTGGCGGCGTGCCTAACACATGCAAGTCGAGCGAAGCGCTGTTTTCAGAATCTTCGGAGGAAGAGGACAGTGACTGAGCGGCGGACGGGTGAGTAACGCGTGGGCAACCTGCCTCATACAGGGGGATAACAGTTAGAAATGACTGCTAATACCGCATAAGCGCACAGGACCGCATGGTGTAGTGTGAAAAACTCCGGTGGTATGAGATGGACCCGCGTCTGATTAGGTAGTTGGTGGGGTAAAGGCCTACCAAGCCGACGATCAGTAGCCGACCTGAGAGGGTGACCGGCCACATTGGGACTGAGACACGGCCCAAACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCTGATGCAGCGACGCCGCGTGAAGGAAGAAGTATTTCGGTATGTAAACTTCTATCAGCAGGGAAGAAGATGACGGTACCTGAGTAAGAAGCACCGGCTAAATACGTGCCAGCAGCCGCGGTAATACGTATGGTGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGAGCGTAGACGGATAGGCAAGTCTGGAGTGAAAACCCAGGGCTCAACTCTGGGACTGCTTTGGAAACTGCAGATCTGGAGTGCCGGAGAGGTAAGCGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCTTACTGGACGGTGACTGACGTTGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGACTACTAGGTGTCGGTGTGCAAAGCACATCGGTGCCGCAGCAAACGCAATAAGTAGTCCACCTGGGGAGTACGTTCGCAAGAATGAAACTCAAAGGAATTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCTGGTCTTGACATCCGGATGACGGGCGAGTAATGTCGCCGTCCCTTCGGGGCATCCGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATCTTCAGTAGCCAGCATATAAGGTGGGCACTCTGGAGAGACTGCCAGGGAGAACCTGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGGCCAGGGCTACACACGTGCTACAATGGCGTAAACAAAGGGAAGCGAGAGGGTGACCTGAAGCGAATCCCAAAAATAACGTCTCAGTTCGGATTGTAGTCTGCAACTCGACTACATGAAGCTGGAATCGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGTCTTGTACACACCGCCCGTCACACCATGGGAGTCAGTAACGCCCGAAGCCANTGACCCAACCTTAGAGGAGGGAGNNNNNNNNNNNNNstrain 26 1A1_27Fmod-PREMIX_Length_998 SEQ ID NO: 26AGTTTGATTATGGCTCAGGATGAACGCTGGCGGCATGCCTAATACATGCAAGTCGAACGAAGTTTCGAGGAAGCTTGCTTCCAAAGAGACTTAGTGGCGAACGGGTGAGTAACACGTAGGTAACCTGCCCATGTGTCCGGGATAACTGCTGGAAACGGTAGCTAAAACCGGATAGGTATACAGAGCGCATGCTCAGTATATTAAAGCGCCCATCAAGGCGTGAACATGGATGGACCTGCGGCGCATTAGCTAGTTGGTGAGGTAACGGCCCACCAAGGCGATGATGCGTAGCCGGCCTGAGAGGGTAAACGGCCACATTGGGACTGAGACACGGCCCAAACTCCTACGGGAGGCAGCAGTAGGGAATTTTCGTCAATGGGGGAAACCCTGAACGAGCAATGCCGCGTGAGTGAAGAAGGTCTTCGGATCGTAAAGCTCTGTTGTAAGTGAAGAACGGCTCATAGAGGAAATGCTATGGGAGTGACGGTAGCTTACCAGAAAGCCACGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGTGGCAAGCGTTATCCGGAATCATTGGGCGTAAAGGGTGCGTAGGTGGCGTACTAAGTCTGTAGTAAAAGGCAATGGCTCAACCATTGTAAGCTATGGAAACTGGTATGCTGGAGTGCAGAAGAGGGCGATGGAATTCCATGTGTAGCGGTAAAATGCGTAGATATATGGAGGAACACCAGTGGCGAAGGCGGTCGCCTGGTCTGTAACTGACACTGAGGCACGAAAGCGTGGGGAGCAAATAGGATTAGATACCCTAGTAGTCCACGCCGTAAACGATGAGAACTAAGTGTTGGAGGAATTCAGTGCTGCAGTTAACGCAATAAGTTCTCCGCCTGGGGAGTATGCACGCAAGTGTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGCCTTGACATGGAAACAAATACCCTAGAGATAGGGGGATAATTATGGATCACACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTGTCGCATGTTACCAGCATCAAGTTGGGGACTCATGCGAGACTGCCGGTGACAAACCGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGGCCTGGGCTACACACGTACTACAATGGCGACCACAAAGAGCAGCGACACAGTGATGTGAAGCGAATCTCATAAAGGTCGTCTCAGTTCGGATTGAAGTCTGCAACTCGACTTCATGAAGTCGGAATCGCTAGTAATCGCAGATCAGCATGCTGCGGTGAATACGTTCTCGGGCCTTGTACACACCGCCCGTCAAACCATGGGAGTCAGTAATACCCGAAGCCGGTGGCATAACCNTAAGGNNNNNCCNNNNNNASEQ ID NO: 27 16S RNA sequence corresponding to LN998073 SEQ ID NO: 2816S RNA sequence corresponding to KR822463 SEQ ID NO: 2916S RNA sequence corresponding to CP011531 SEQ ID NO: 3016S RNA sequence corresponding to NR112945 SEQ ID NO: 3116S RNA sequence corresponding to KM098109 SEQ ID NO: 3216S RNA sequence corresponding to NR113078 SEQ ID NO: 3316S RNA sequence corresponding to NR041464 SEQ ID NO: 3416S RNA sequence corresponding to LT223566 SEQ ID NO: 3516S RNA sequence corresponding to NR112835 SEQ ID NO: 3616S RNA sequence corresponding to NR113248 SEQ ID NO: 3716S RNA sequence corresponding to NR041342 SEQ ID NO: 3816S RNA sequence corresponding to NR112933 SEQ ID NO: 3916S RNA sequence corresponding to NR112893 SEQ ID NO: 4016S RNA sequence corresponding to HE974918 SEQ ID NO: 4116S RNA sequence corresponding to NR043016 SEQ ID NO: 4216S RNA sequence corresponding to AB618791 SEQ ID NO: 4316S RNA sequence corresponding to AB215083 SEQ ID NO: 4416S RNA sequence corresponding to NR112935 SEQ ID NO: 4516S RNA sequence corresponding to AB249652 SEQ ID NO: 4616S RNA sequence corresponding to NR113076 SEQ ID NO: 4716S RNA sequence corresponding to NR112944 SEQ ID NO: 4816S RNA sequence corresponding to JX519760 SEQ ID NO: 4916S RNA sequence corresponding to AJ311620 SEQ ID NO: 5016S RNA sequence corresponding to EF564278 SEQ ID NO: 5116S RNA sequence corresponding to KT156811 SEQ ID NO: 5216S RNA sequence corresponding to HM008265

Additional sequences of interest are provided below:

H81A6_16S_ribosomal_RNA SEQ ID NO: 54CGAAGAGTTTGATCCTGGCTCAGGATGAACGCTGACAGAATGCTTAACACATGCAAGTCTACTTGATCCTTCGGGTGAAGGTGGCGGACGGGTGAGTAACGCGTAAAGAACTTGCCTTACAGACTGGGACAACATTTGGAAACGAATGCTAATACCGGATATTATGATTGGGTCGCATGATCTGATTATGAAAGCTATATGCGCTGTGAGAGAGCTTTGCGTCCCATTAGTTAGTTGGTGAGGTAACGGCTCACCAAGACGATGATGGGTAGCCGGCCTGAGAGGGTGAACGGCCACAAGGGGACTGAGACACGGCCCTTACTCCTACGGGAGGCAGCAGTGGGGAATATTGGACAATGGACCAAAAGTCTGATCCAGCAATTCTGTGTGCACGAAGAAGTTTTTCGGAATGTAAAGTGCTTTCAGTTGGGAAGAAGTCAGTGACGGTACCAACAGAAGAAGCGACGGCTAAATACGTGCCAGCAGCCGCGGTAATACGTATGTCGCAAGCGTTATCCGGATTTATTGGGCGTAAAGCGCGTCTAGGCGGCTTAGTAAGTCTGATGTGAAAATGCGGGGCTCAACCCCGTATTGCGTTGGAAACTGCTAAACTAGAGTACTGGAGAGGTAGGCGGAACTACAAGTGTAGAGGTGAAATTCGTAGATATTTGTAGGAATGCCGATGGGGAAGCCAGCCTACTGGACAGATACTGACGCTAAAGCGCGAAAGCGTGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGATTACTAGGTGTTGGGGGTCGAACCTCAGCGCCCAAGCTAACGCGATAAGTAATCCGCCTGGGGAGTACGTACGCAAGTATGAAACTCAAAGGAATTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGACGCAACGCGAGGAACCTTACCAGCGTTTGACATCCCAAGAAGTTAACAGAGATGTTTTCGTGCCTCTTCGGAGGAACTTGGTGACAGGTGGTGCATGGCTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCCTTTCGTATGTTACCATCATTAAGTTGGGGACTCATGCGAGACTGCCTGCGATGAGCAGGAGGAAGGTGGGGATGACGTCAAGTCATCATGCCCCTTATACGCTGGGCTACACACGTGCTACAATGGGTAGTACAGAGAGCTGCAAACCTGCGAGGGTAAGCTAATCTCATAAAACTATTCTTAGTTCGGATTGTACTCTGCAACTCGAGTACATGAAGTTGGAATCGCTAGTAATCGCAAATCAGCTATGTTGCGGTGAATACGTTCTCGGGTCTTGTACACACCGCCCGTCACACCACGAGAGTTGGTTGCACCTGAAGTAACAGGCCTAACCGTAAGGAGGGATGTTCCGAGGGTGTGATTAGCGATTGGGGTGAAGTCGTAACAAGGTATCCGTACGGGAACGTGCGGATGGATCACCTCCTT H82F11_16S_ribosomal_RNA SEQ ID NO: 55CGAAGAGTTTGATCCTGGCTCAGGATGAACGCTAGCGACAGGCTTAACACATGCAAGTCGAGGGGCATCATGGTAAGTAGCAATACTTATTGATGGCGACCGGCGCACGGGTGAGTAACGCGTATGCAACTTACCTATCAGAGGGGGATAGCCCGGCGAAAGTCGGATTAATACTCCATAAAACAGGGGTTCCGCATGGGACTATTTGTTAAAGATTCATCGCTGATAGATAGGCATGCGTTCCATTAGGCAGTTGGCGGGGTAACGGCCCACCAAACCGACGATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGTACTGAGACACGGACCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGCCGAGAGGCTGAACCAGCCAAGTCGCGTGAAGGATGAAGGATCTATGGTTTGTAAACTTCTTTTATAGGGGAATAAAGTGTGGGACGTGTTCCATTTTGTATGTACCCTATGAATAAGCATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATGCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGTGCGTAGGTGGTAATTTAAGTCAGCGGTGAAAGTTTGTGGCTCAACCATAAAATTGCCGTTGAAACTGGGTTACTTGAGTGTGTTTGAGGTAGGCGGAATGCGTGGTGTAGCGGTGAAATGCATAGATATCACGCAGAACTCCAATTGCGAAGGCAGCTTACTAAACCATAACTGACACTGAAGCACGAAAGCGTGGGTATCAAACAGGATTAGATACCCTGGTAGTCCACGCAGTAAACGATGATTACTAGGAGTTTGCGATACACAGTAAGCTCTACAGCGAAAGCGTTAAGTAATCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACCTTACCCGGGTTTGAACGTAGTCAGACCGACCTTGAAAGAGGTTTTCTAGCAATAGCTGATTACGAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTATCACTAGTTACTAACAGGTTAAGCTGAGGACTCTGGTGAGACTGCCAGCGTAAGCTGTGAGGAAGGTGGGGATGACGTCAAATCAGCACGGCCCTTACATCCGGGGCGACACACGTGTTACAATGGCATGGACAAAGGGCAGCTACCTGGCGACAGGATGCTAATCTCTAAACCATGTCTCAGTTCGGATCGGAGTCTGCAACTCGACTCCGTGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGGGAGCCGGGGGTACCTGAAGTCCGTAACCGCAAGGATCGGCCTAGGGTAAAACTGGTGACTGGGGCTAAGTCGTAACAAGGTAGCCGTACCGGAAGGTGCGGCTGGAACACCTCCTT H82A6_16S_ribosomal_RNASEQ ID NO: 56AATAAAGATTAATTGGTAAAGGATGGGGATGCGTCCCATTAGCTTGTTGGCGGGGTAACGGCCCACCAAGGCGACGATGGGTAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGGCGCGAGCCTGAACCAGCCAAGTAGCGTGGAGGACGACGGCCCTACGGGTTGTAAACTCCTTTTATAAGGGGATAAAGTTGGCCATGTATGGCCATTTGCAGGTACCTTATGAATAAGCATCGGCTAATTCCGTGCCAGCAGCCGCGGTAATACGGAAGATGCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGAGCGTAGGCGGGCAGTCAAGTCAGCGGTCAAATGGCGCGGCTCAACCGCGTTCCGCCGTTGAAACTGGCAGCCTTGAGTATGCACAGGGTACATGGAATTCGTGGTGTAGCGGTGAAATGCTTAGATATCACGAGGAACTCCGATCGCGCAGGCATTGTACCGGGGCATTACTGACGCTGAGGCTCGAAGGTGCGGGTATCAAACAGGATTAGATACCCTGGTAGTCCGCACAGTAAACGATGAATGCCCGCTGTCGGCGACATAGTGTCGGCGGCCAAGCGAAAGCGTTAAGCATTCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACCTTACCCGGGCTTGAATCGCAGGTGCATGGGCCGGAGACGGCCCTTTCCTTCGGGACTCCTGCGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCCCCTCCCCAGTTGCCACCGGGTAATGCCGGGCACTTTGGGGACACTGCCACCGCAAGGTGCGAGGAAGGTGGGGATGACGTCAAATCAGCACGGCCCTTACGTCCGGGGCGACACACGTGTTACAATGGGGGGTACAGAGGGCCGCTGCCCGGTGACGGTTGGCCAATCCCTAAAACCCCTCTCAGTTCGGACTGGAGTCTGCAACCCGACTCCACGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGAAAGCCGGGGGTGCCTGAAGTCCGTGACCGCGAGGGTCGGCCTAGGGTAAAACCGGTGATTGGGGCTAAGTCGTAACAAGGTAGCCGTACCGGAAGGTGCGGCTGGAACACCTCCTTT H82G9_16S_ribosomal_RNA SEQ ID NO: 57CGAAGAGTTTGATCCTGGCTCAGGATGAACGCTAGCGACAGGCTTAACACATGCAAGTCGAGGGGCAGCACAGGTAGCAATACCGGGTGGCGACCGGCGCACGGGTGAGTAACGCGTATGCAACTTGCCTATCAGAGGGGGATAACCCGGCGAAAGTCGGACTAATACCGCATGAAGCAGGGGCCCCGCATGGGGATATTTGCTAAAGATTCATCGCTGATAGATAGGCATGCGTTCCATTAGGCAGTTGGCGGGGTAACGGCCCACCAAACCGACGATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGTACTGAGACACGGACCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGCCGAGAGGCTGAACCAGCCAAGTCGCGTGAGGGATGAAGGTTCTATGGATCGTAAACCTCTTTTATAAGGGAATAAAGTGCGGGACGTGTCCCGTTTTGTATGTACCTTATGAATAAGGATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGTGCGTAGGCGGCCTTTTAAGTCAGCGGTGAAAGTCTGTGGCTCAACCATAGAATTGCCGTTGAAACTGGGGGGCTTGAGTATGTTTGAGGCAGGCGGAATGCGTGGTGTAGCGGTGAAATGCATAGATATCACGCAGAACCCCGATTGCGAAGGCAGCCTGCCAAGCCATTACTGACGCTGATGCACGAAAGCGTGGGGATCAAACAGGATTAGATACCCTGGTAGTCCACGCAGTAAACGATGATCACTAGCTGTTTGCGATACACTGTAAGCGGCACAGCGAAAGCGTTAAGTGATCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACCTTACCCGGGTTTGAACGCATTCGGACCGAGGTGGAAACACCTTTTCTAGCAATAGCCGTTTGCGAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTGCCACTAGTTACTAACAGGTAAAGCTGAGGACTCTGGTGGGACTGCCAGCGTAAGCTGCGAGGAAGGCGGGGATGACGTCAAATCAGCACGGCCCTTACATCCGGGGCGACACACGTGTTACAATGGCGTGGACAAAGGGAAGCCACCTGGCGACAGGGAGCGAATCCCCAAACCACGTCTCAGTTCGGATCGGAGTCTGCAACCCGACTCCGTGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGGGAGCCGGGGGTACCTGAAGTCCGTAACCGCGAGGATCGGCCTAGGGTAAAACTGGTGACTGGGGCTAAGTCGTAACAAGGTAGCCGTACCGGAAGGTGCGGCTGGAACACCTCCTTT H81E7_16S_ribosomal_RNASEQ ID NO: 58ATGGAGAGTTTGATCCTGGCTCAGGATGAACGCTAGCGGCAGGCCTAACACATGCAAGTCGAGGGGCAGCGGGATTGAAGCTTGCTTCAGTTGCCGGCGACCGGCGCACGGGTGCGTAACGCGTATGCAACCTACCCATAACAGGGGGATAACACTGAGAAATCGGTACTAATATCCCATAACATCAAGAGGGGCATCCCTTTTGGTTGAAAACTCCGGTGGTTATGGATGGGCATGCGTTGTATTAGCTAGTTGGTGAGGTAACGGCTCACCAAGGCGACGATACATAGGGGGACTGAGAGGTTAACCCCCCACATTGGTACTGAGACACGGACCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGACGCAAGTCTGAACCAGCCATGCCGCGTGCAGGATGACGGCTCTATGAGTTGTAAACTGCTTTTGTACGAGGGTAAACCCGGATACGTGTATCCGGCTGAAAGTATCGTACGAATAAGGATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATTCAAGCGTTATCCGGATTTATTGGGTTTAAAGGGTGCGTAGGCGGTTTGATAAGTTAGAGGTGAAATACCGGTGCTTAACACCGGAACTGCCTCTAATACTGTTGAGCTAGAGAGTAGTTGCGGTAGGCGGAATGTATGGTGTAGCGGTGAAATGCTTAGAGATCATACAGAACACCGATTGCGAAGGCAGCTTACCAAACTATATCTGACGTTGAGGCACGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCAGTAAACGATGATAACTCGCTGTCGGCGATACACAGTCGGTGGCTAAGCGAAAGCGATAAGTTATCCACCTGGGGAGTACGTTCGCAAGAATGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACCTTACCCGGGCTTGAAAGTTACTGACGATTCTGGAAACAGGATTTCCCTTCGGGGCAGGAAACTAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGGTTAAGTCCCATAACGAGCGCAACCCCTACCGTTAGTTGCCATCAGGTCAAGCTGGGCACTCTGGCGGGACTGCCGGTGTAAGCCGAGAGGAAGGTGGGGATGACGTCAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGTAGGTACAGAGGGCAGCTACCCAGTGATGGGATGCGAATCTCGAAAGCCTATCTCAGTTCGGATTGGAGGCTGAAACCCGCCTCCATGAAGTTGGATTCGCTAGTAATCGCGCATCAGCCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGGAAGCTGGGGGTGCCTGAAGTTCGTGACCGCAAGGAGCGACCTAGGGCAAAACCGGTGACTGGGGCTAAGTCGTAACAAGGTAGCCGTACCGGAAGGTGCGGCTGGAACACCTCCTTT H81C1_16S_ribosomal_RNASEQ ID NO: 59TATTGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGTATGCTTAACACATGCAAGTCGAACGAGAAGGTTTTGATGGATCCTTCGGGTGATATCAGAACTGGAAAGTGGCGAACGGGTGAGTAACGCGTGGGTAACCTGCCCTATGGAAAGGAATAGCCTCGGGAAACTGGGAGTAAAGCCTTATATTATGGTTTTGTCGCATGGCAAGATCATGAAAACTCCGGTGCCATAGGATGGACCCGCGTCCCATTAGCTAGTTGGTGAGATAACAGCCCACCAAGGCGACGATGGGTAACCGGTCTGAGAGGGCGAACGGTCACACTGGAACTGAGACACGGTCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCGCAATGGGGGCAACCCTGACGCAGCAATACCGCGTGAGTGAAGAAGGTTTTCGGATCGTAAAGCTCTGTTATTGGGGAAGAAGAATGACGGTACCCAATGAGGAAGTCCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGGACAAGCGTTGTCCGGAATGACTGGGCGTAAAGGGCGCGTAGGCGGTCTATTAAGTCTGATGTGAAAGGTACCGGCTCAACCGGTGAAGTGCATTGGAAACTGGTAGACTTGAGTATTGGAGAGGCAAGTGGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCTTGCTGGACAAATACTGACGCTGAGGTGCGAAAGCGTGGGGAGCGAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGAATGCTAGGTGTTGGGGAAACTCAGTGCCGCAGTTAACACAATAAGCATTCCGCCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACGGGGACCCGCACAAGCAGCGGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACATCCTCTGACGAGCCTAGAGATAGGAAGTTTCCTTCGGGAACAGAGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCCTGCCTTTAGTTGCCAGCATTAAGTTGGGCACTCTAGAGGGACTGCCGTAGACAATACGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACACGTGCTACAATGGTCTGAACAGAGGGCCGCGAAGCCGCGAGGTGAAGCAAATCCCTTAAAACAGATCCCAGTTCGGATTGCAGGCTGCAACTCGCCTGCATGAAGTTGGAGTTGCTAGTAATCGCGGATCAGAATGCCGCGGTGAATGCGTTCCCGGGTCTTGTACACACCGCCCGTCACACCACGAGAGTTGGCAACACCCGAAGCCTGTGAGAGAACCGTAAGGACTCAGCAGTCGAAGGTGGGGCTAGTAATTGGGGTGAAGTCGTAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT H81B11_16S_ribosomal_RNASEQ ID NO: 60ATGAAGAGTTTGATCCTGGCTCAGGATGAACGCTAGCTACAGGCTTAACACATGCAAGTCGAGGGGCAGCATGGTCTTAGCTTGCTAAGGCTGATGGCGACCGGCGCACGGGTGAGTAACACGTATCCAACCTGCCGTCTACTCTTGGCCAGCCTTCTGAAAGGAAGATTAATCCAGGATGGGATCATGAGTTCACATGTCCGCATGATTAAAGGTATTTTCCGGTAGACGATGGGGATGCGTTCCATTAGATAGTAGGCGGGGTAACGGCCCACCTAGTCAACGATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGGCGATGGCCTGAACCAGCCAAGTAGCGTGAAGGATGACTGCCCTATGGGTTGTAAACTTCTTTTATAAAGGAATAAAGTCGGGTATGCATACCCGTTTGCATGTACTTTATGAATAAGGATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGAGCGTAGATGGATGTTTAAGTCAGTTGTGAAAGTTTGCGGCTCAACCGTAAAATTGCAGTTGATACTGGATGTCTTGAGTGCAGTTGAGGCAGGCGGAATTCGTGGTGTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAGCCTGCTAAGCTGCAACTGACATTGAGGCTCGAAAGTGTGGGTATCAAACAGGATTAGATACCCTGGTAGTCCACACGGTAAACGATGAATACTCGCTGTTTGCGATATACGGCAAGCGGCCAAGCGAAAGCGTTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACCTTACCCGGGCTTAAATTGCACTCGAATGATCCGGAAACGGTTCAGCTAGCAATAGCGAGTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTGTTGTCAGTTACTAACAGGTGATGCTGAGGACTCTGACAAGACTGCCATCGTAAGATGTGAGGAAGGTGGGGATGACGTCAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGGGGGTACAGAGGGCCGCTACCACGCGAGTGGATGCCAATCCCTAAAACCCCTCTCAGTTCGGACTGGAGTCTGCAACCCGACTCCACGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCACGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGGGAGCCGGGGGTACCTGAAGTGCGTAACCGCGAGGATCGCCCTAGGGTAAAACTGGTGACTGGGGCTAAGTCGTAACAAGGTAGCCGTACCGGAAGGTGCGGCTGGAACACCTCCTTH81H9_16S_ribosomal_RNA SEQ ID NO: 61CGAAGAGTTTGATCCTGGCTCAGGATGAACGCTAGCGACAGGCTTAACACATGCAAGTCGAGGGGCAGCAGGAAGTAGCAATACTTTGCTGGCGACCGGCGCACGGGTGAGTAACGCGTATGCAACCTACCTATCAGAGGGGGATAACCCGGCGAAAGTCGGACTAATACCGCATAAAACAGGGGTCCCGCATGGGAATATTTGTTAAAGATTTATTGCTGATAGATGGGCATGCGTTCCATTAGATAGTTGGTGAGGTAACGGCTCACCAAGTCTTCGATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACACTGGTACTGAGACACGGACCAGACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGGCGAGAGCCTGAACCAGCCAAGTCGCGTGAAGGATGAAGGATCTATGGTTCGTAAACTTCTTTTATAGGGGAATAAAGTGCAGGACGTGTCCTGTTTTGTATGTACCCTATGAATAAGGATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGTGCGTAGGTGGCTTTTTAAGTCAGCGGTGAAAGTTTGTGGCTCAACCATAAAATTGCCGTTGAAACTGGAGGGCTTGAGTATATTTGAGGTAGGCGGAATGCGTGGTGTAGCGGTGAAATGCATAGATATCACGCAGAACTCCAATTGCGAAGGCAGCTTACTAAACTATAACTGACACTGAAGCACGAAAGCGTGGGGATCAAACAGGATTAGATACCCTGGTAGTCCACGCAGTAAACGATGATTACTAGGAGTTTGCGATACACAGTAAGCTCTACAGCGAAAGCGTTAAGTAATCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACCTTACCCGGGTTTGAACGTAAGTTGACCGGAGTGGAAACACTCTTTCTAGCAATAGCAATTTACGAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTATCTTTAGTTACTAACAGGTCGAGCTGAGGACTCTAAAGAGACTGCCAGCGTAAGCTGTGAGGAAGGTGGGGATGACGTCAAATCAGCACGGCCCTTACATCCGGGGCGACACACGTGTTACAATGGTGGGGACAAAGGGCAGCTACCTGGCGACAGGATGCTAATCTCCAAACCCCATCTCAGTTCGGATCGAAGTCTGCAACCCGACTTCGTGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGGGAGTTGGGGGTACCTAAAGTCCGTAACCGCAAGGATCGGCCTAGGGTAAAACCGATGACTGGGGCTAAGTCGTAACAAGGTAGCCGTACCGGAAGGTGCGGCTGGAACACCTCCTTT H82B1_16S_ribosomal_RNASEQ ID NO: 62AATGAAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGCGCCTAACACATGCAAGTCGAACGGAGCTGTTTTCTCTGAAGTTTTCGGATGGAAGAGAGTTCAGCTTAGTGGCGAACGGGTGAGTAACACGTGAGCAACCTGCCTTTCAGTGGGGGACAACATTTGGAAACGAATGCTAATACCGCATAAGACCACAGTGTCGCATGGCACAGGGGTCAAAGGATTTATCCGCTGAAAGATGGGCTCGCGTCCGATTAGCTAGATGGTGAGGTAACGGCCCACCATGGCGACGATCGGTAGCCGGACTGAGAGGTTGAACGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCTGATGCAGCGACGCCGCGTGGAGGAAGAAGGTCTTCGGATTGTAAACTCCTGTCCCAGGGGACGATAATGACGGTACCCTGGGAGGAAGCACCGGCTAACTACGTGCCAGCAGCCGCGGTAAAACGTAGGGTGCAAGCGTTGTCCGGAATTACTGGGTGTAAAGGGAGCGCAGGCGGATTGGCAAGTTGGGAGTGAAATCTATGGGCTCAACCCATAAATTGCTTTCAAAACTGTCAGTCTTGAGTGGTGTAGAGGTAGGCGGAATTCCCGGTGTAGCGGTGGAATGCGTAGATATCGGGAGGAACACCAGTGGCGAAGGCGGCCTACTGGGCACTAACTGACGCTGAGGCTCGAAAGCATGGGTAGCAAACAGGATTAGATACCCTGGTAGTCCATGCCGTAAACGATGATTACTAGGTGTGGGAGGATTGACCCCTTCCGTGCCGCAGTTAACACAATAAGTAATCCACCTGGGGAGTACGACCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCAGTGGAGTATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACATCGGATGCATACCTAAGAGATTAGGGAAGTCCTTCGGGACATCCAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATCGTTAGTTACTACGCAAGAGGACTCTAGCGAGACTGCCGTTGACAAAACGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCTTTATGACCTGGGCTACACACGTACTACAATGGCTATTAACAGAGAGAAGCGATACCGCGAGGTGGAGCAAACCTCACAAAAATAGTCTCAGTTCGGATCGCAGGCTGCAACCCGCCTGCGTGAAGCCGGAATTGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCACACCATGAGAGCCGGGGGGACCCGAAGTCGGTAGTCTAACCGCAAGGAGGACGCCGCCGAAGGTAAAACTGGTGATTGGGGTGAAGTCGTAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT H82G1_16S_ribosomal_RNASEQ ID NO: 63ATGAAGAGTTTGATCCTGGCTCAGGATGAACGCTAGCTACAGGCTTAACACATGCAAGTCGAGGGGCAGCATGAACTTAGCTTGCTAAGTTTGATGGCGACCGGCGCACGGGTGAGTAACACGTATCCAACCTGCCGATGACTCGGGGATAGCCTTTCGAAAGAAAGATTAATACCCGATGGCATAGTTCTTCCGCATGGTGGAACTATTAAAGAATTTCGGTCATCGATGGGGATGCGTTCCATTAGGTTGTTGGCGGGGTAACGGCCCACCAAGCCTTCGATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGACGAGAGTCTGAACCAGCCAAGTAGCGTGAAGGATGACTGCCCTATGGGTTGTAAACTTCTTTTATACGGGAATAAAGTGAGGCACGTGTGCCTTTTTGTATGTACCGTATGAATAAGGATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATCCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGAGCGTAGGCGGACGCTTAAGTCAGTTGTGAAAGTTTGCGGCTCAACCGTAAAATTGCAGTTGATACTGGGTGTCTTGAGTACAGTAGAGGCAGGCGGAATTCGTGGTGTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAGCCTGCTGGACTGTAACTGACGCTGATGCTCGAAAGTGTGGGTATCAAACAGGATTAGATACCCTGGTAGTCCACACAGTAAACGATGAATACTCGCTGTTTGCGATATACAGTAAGCGGCCAAGCGAAAGCGTTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACCTTACCCGGGCTTGAATTGCAACTGAATGATGTGGAGACATGTCAGCCGCAAGGCAGTTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCTTATCGATAGTTACCATCAGGTGATGCTGGGGACTCTGTCGAGACTGCCGTCGTAAGATGTGAGGAAGGTGGGGATGACGTCAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGGGGGTACAGAAGGCAGCTACACGGCGACGTGATGCTAATCCCGAAAGCCTCTCTCAGTTCGGATTGGAGTCTGCAACCCGACTCCATGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCACGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGAAAGCCGGGGGTACCTGAAGTGCGTAACCGCAAGGAGCGCCCTAGGGTAAAACTGGTGATTGGGGCTAAGTCGTAACAAGGTAGCCGTACCGGAAGGTGCGGCTGGAACACCTCCTT H82G5_16S_ribosomal_RNASEQ ID NO: 64ATTGGAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCCTAACACATGCAAGTCGAACGGAGAATTTTATTTCGGTAGAATTCTTAGTGGCGAACGGGTGAGTAACGCGTAGGCAACCTACCCTTTAGACGGGGACAACATTCCGAAAGGAGTGCTAATACCGGATGTGATCATCTTGCCGCATGGCAGGATGAAGAAAGATGGCCTCTACAAGTAAGCTATCGCTAAAGGATGGGCCTGCGTCTGATTAGCTAGTTGGTAGTGTAACGGACTACCAAGGCGATGATCAGTAGCCGGTCTGAGAGGATGAACGGCCACATTGGGACTGAGACACGGCCCAAACTCCTACGGGAGGCAGCAGTGGGGAATCTTCCGCAATGGACGAAAGTCTGACGGAGCAACGCCGCGTGAGTGATGAAGGATTTCGGTCTGTAAAGCTCTGTTGTTTATGACGAACGTGCAGTGTGTGAACAATGCATTGCAATGACGGTAGTAAACGAGGAAGCCACGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGTGGCGAGCGTTGTCCGGAATTATTGGGCGTAAAGAGCATGTAGGCGGCTTAATAAGTCGAGCGTGAAAATGCGGGGCTCAACCCCGTATGGCGCTGGAAACTGTTAGGCTTGAGTGCAGGAGAGGAAAGGGGAATTCCCAGTGTAGCGGTGAAATGCGTAGATATTGGGAGGAACACCAGTGGCGAAGGCGCCTTTCTGGACTGTGTCTGACGCTGAGATGCGAAAGCCAGGGTAGCGAACGGGATTAGATACCCCGGTAGTCCTGGCCGTAAACGATGGGTACTAGGTGTAGGAGGTATCGACCCCTTCTGTGCCGGAGTTAACGCAATAAGTACCCCGCCTGGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGTGGAGTATGTGGTTTAATTCGACGCAACGCGAAGAACCTTACCAAGGCTTGACATTGATTGAACGCTCTAGAGATAGAGATTTCCCTTCGGGGACAAGAAAACAGGTGGTGCATGGCTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCCTATCCTATGTTACCAGCAAGTAAAGTTGGGGACTCATGGGAGACTGCCAGGGACAACCTGGAGGAAGGCGGGGATGACGTCAAGTCATCATGCCCCTTATGTCTTGGGCTACACACGTACTACAATGGTCGGAAACAGAGGGAAGCGAAGCCGCGAGGCAGAGCAAACCCCAGAAACCCGATCTCAGTTCGGATCGCAGGCTGCAACCCGCCTGCGTGAAGTCGGAATCGCTAGTAATCGCAGGTCAGCATACTGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCACACCACGAAAGTTGGTAACACCCGAAGCCGGTGAGGTAACCTATTAGGAGCCAGCCGTCTAAGGTGGGGCCGATGATTGGGGTGAAGTCGTAACAAGGTAGCCGTATCGGAAGGTGCGGCTGGATCACCTCCTTT

The invention is not limited in its application to the details ofconstruction and the arrangement of components set forth in thefollowing description or illustrated in the drawings. The invention iscapable of other embodiments and of being practiced or of being carriedout in various ways. Also, the phraseology and terminology used hereinis for the purpose of description and should not be regarded aslimiting. The use of “including,” “comprising,” or “having,”“containing,” “involving,” and variations thereof herein, is meant toencompass the items listed thereafter and equivalents thereof as well asadditional items. Unless otherwise defined herein, scientific andtechnical terms used in connection with the present disclosure shallhave the meanings that are commonly understood by those of ordinaryskill in the art. Further, unless otherwise required by context,singular terms shall include pluralities and plural terms hall includethe singular. The methods and techniques of the present disclosure aregenerally performed according to conventional methods well-known in theart. Generally, nomenclatures used in connection with, and techniques ofbiochemistry, enzymology, molecular and cellular biology, microbiology,virology, cell or tissue culture, genetics and protein and nucleicchemistry described herein are those well-known and commonly used in theart. The methods and techniques of the present disclosure are generallyperformed according to conventional methods well known in the art and asdescribed in various general and more specific references that are citedand discussed throughout the present specification unless otherwiseindicated.

The present invention is further illustrated by the following Examples,which in no way should be construed as further limiting. The entirecontents of all of the references (including literature references,issued patents, published patent applications, and co-pending patentapplications) cited throughout this application are hereby expresslyincorporated by reference, in particular for the teaching that isreferenced hereinabove. However, the citation of any reference is notintended to be an admission that the reference is prior art.

EXAMPLES Example 1: Identification of a CD8+ T-Cell Inducing BacterialCocktail

C57BL/6 mice kept under specific-pathogen free (SPF) conditions whichpossess resident microbiota have abundant IFNγ+CD8+ T-cells, whereasmarkedly few IFNγ+CD8+ T-cells were found in intestinal lamina propriaof germ free mice (See FIG. 1). This indicates that gut microbiotainduces the accumulation of IFNγ+CD8+ T-cells. A subset of IFNγ+CD8+ Tcells also expressed CD103 as well as GranzymeB (see FIG. 2A),suggesting that the subset was tissue-resident memory T cells. FIG. 3Ashows that remarkably small numbers of IFNγ+CD8+ T-cells were found inSPF C57BL/6 mice purchased from Charles River Laboratories Inc. andJapan SLC Inc. as compared to SPF C57BL/6 mice purchased from CLEA JapanInc. and mice bred in RIKEN. When SPF C57BL/6 mice from Charles RiverLaboratories Inc. were co-housed together with CLEA mice in the samecage, an increase of IFNγ+CD8+ T-cells was observed in mice deliveredfrom Charles River Laboratories Inc. (FIGS. 4A and 4B). This findingstrongly supports a hypothesis that there are specific microbial speciesin the mouse microbiota which induce and accumulate IFNγ+CD8+ T cells inthe intestine.

Next, it was investigated whether the human gut microbiota containedmicrobes which were able to induce IFNγ+CD8+ T cells. Stool samples werecollected from six healthy human volunteers (A˜F). The samples wereindividually administered orally into germ free C57BL/6 mice kept insterile isolators (five or six mice per group). Four weeks after oralinoculation of stool samples, mice were sacrificed, and small intestineand colons were harvested and investigated for IFNγ+CD8+ T-cells byFACS. As shown in FIGS. 5A and 5B, colonic IFNγ+CD8+ T-cells were mostremarkably induced in mice inoculated with a stool sample collected fromdonor B. Among mice inoculated with the donor B stool sample, weselected a mouse that exhibited the highest frequency of IFNγ+CD8+ Tcells (called ‘mouse B #5’ hereafter). In order to concentrate microbesresponsible for IFNγ+CD8+ T cell induction, cecal contents werecollected from the mouse B #5 and inoculated into another germ-freemouse. The mice were then orally administrated drinking water with orwithout Ampicillin, Metronidazole, Streptomycin or Tylosin (five miceper group). Alternatively, cecal contents of mouse B #5 were treatedwith 3% chloroform and orally inoculated into another five germ-freemice (‘B #5+Chrolo’). FIGS. 6A and 6B show that Ampicillin treatmentenhanced induction of colonic lamina propria IFNγ+CD8+ T-cells by themouse B #5 microbiota, whereas other antibiotics treatment or chloroformtreatment reduced the induction capability of IFNγ+CD8+ T-Cells by themouse B #5 microbiota.

FIGS. 7A and 7B show the operational taxonomic unit (OTU) analysis ofintestinal contents of mice inoculated with mouse B #5 microbiota andtreated with/without antibiotics or chloroform. Cecal contents werecollected from two B #5+AMP mice that exhibited the highest frequency ofIFNγ+CD8+ T cells (mouse B #5+AMP-2 and mouse B #5+AMP-3) and culturedin an anaerobic chamber. 304 colonies were picked and sequencing of the16S rRNA gene revealed that 26 strains were isolated. Twenty-one strainswere selected from the 26 strains, excluding 5 strains which wereincluded in the microbiota of B #5+Chrolo mice (therefore predicted tobe unnecessary for induction of IFNγ+CD8+ T-cells). The mixture of 21strains was orally inoculated into germ free mice and strong inductionof IFNγ+CD8+ T-cells was observed (FIGS. 8A and 8B). IFNγ+CD8+ T cellsinduced by the 21 strains also expressed CD103 and a part of theIFNγ+CD8+ T-cells expressed Granzyme B as well (FIGS. 9A and 9B). Amixture of 11 strains with the highest correlation with IFNγ+CD8+T-cells was inoculated into GF mice as well. The mixture of 11 strains(11 mix) was orally a strong induction of IFNγ+CD8+ T-cells, even whencompared to the 21 strains mixture (21 mix) (FIGS. 10A and 10B).Identification of the bacterial species with the highest homology toeach of the strains in the 11 mix is provided in Table 2, below.

TABLE 2 Mixture of 11 strains NCBI SEQ ID of accession # NCBI 16S Strain# SEQ ID NO Strain ID Species with highest homology of 16S locus locus 11 2G5 Phascolarctobacterium faecium LN998073 27 2 2 1A6 Fusobacteriumulcerans KR822463 28 3 3 1B11 Bacteroides dorei CP011531 29 4 4 2G1Bacteroides uniformis NR112945 30 5 5 2B1 Subdoligranulum sp. KM09810931 6 6 2A6 Paraprevotella xylaniphila NR113078 32 7 7 2F11Parabacteroides johnsonii NR041464 33 8 8 1E7 Alistipes sp. LT223566 349 9 1H9 Parabacteroides gordonii NR112835 35 10 10 1C1 Eubacterumlimosum NR113248 36 11 11 2G9 Parabacteroides distasonis NR041342 37

Example 1A: Further Characterization of the Mixture of 11 Strains(Composition A)

The strains of Table 2 were characterized further by resequencing of the16S sequences and by whole genome sequencing. The results of the furthercharacterization are found in Table 3.

TABLE 3 [Further characterization of the 11-mix (the mixture of 11strains)] SEQ species with highest NCBI species with highest ID Strainhomology based on accession homology based on Strain # NO ID original16S analysis ID 16S resequencing 2 2 1A6 Fusobacterium K0052822463Fusobacterium ulcerans varium 7 7 2F11 Parabacteroides NR041464Parabacteroides johnsonii johnsonii 6 6 2A6 Paraprevotella NR113078Paraprevotella xylaniphila xylaniphila 11 11 2G9 ParabacteroidesNR041342 Parabacteroides distasonis distasonis 8 8 1E7 Alistipes sp.LT223566 Alistipes senegalensis 10 10 1C1 Eubacterium NR113248Eubacterium limosum limosum 3 3 1B11 Bacteroides dorei CP011531Bacteroides dorei 9 9 1H9 Parabacteroides NR112835 Parabacteroidesgordonii gordonii 5 5 2B1 Subdolinogranulum KM098109 Gemminger sp.formicilis 4 4 2G1 Bacteroides NR112945 Bacteroides uniformis uniformis1 1 2G5 Phascolarctobacterium LN998073 Phascolarctobacterium faeciumfaecium 16S species with highest Alternative Identity homology based onWGS WGS species with (%) of whole genome Identity Coverage high(est)Strain # re-sequencing sequencing (WGS) (%) (%) homology 2 99Fusobacterium 93.2 78.6 ulcerans 7 99 Parabacteroides 99.9 90.5johnsonii 6 99 Paraprevotella 98.9 92.1 xylaniphila 11 99Parabacteroides sp. 99.4 95.4 CAG:2 8 99 Alistipes 98.7 72.2 Alistipessenegalensis timonensis 10 99 Eubacterium 95 81 limosum 3 99 Bacteroidesdorei 99.3 79.5 Bacteroides fluxus 9 97 Parabacteroides sp. 90 50HGS0025 5 99 Ruminococcaceae 99.2 73.9 Ruthenibacterium bacterium cv2lactatiformans 4 99 Bacteroides sp. D20 98.5 81 1 99Phascolarctobacterium 99.2 87 sp. CAG:207

Example 2: Further Characterization of a CD8+ T-Cell Inducing BacterialCocktail

Twenty six strains isolated from cecal contents of B #5+AMP mice thatexhibited high frequencies of IFNγ+CD8+ T cells are shown in FIG. 11.Among the 26 strains, 11 strains (“11 mix”) were positively correlatedwith the frequency of IFNγ+CD8+ T cells. Therefore, these 11 strainswere selected for further experiments, and the mixture of 11 strains(“11-mix”) was inoculated into germ-free mice (see also Table 2).Colonization with the 11-mix resulted in a strong induction of colonicIFNγ+CD8+ T cells (FIGS. 10A, 10B, 12A, and 12B), whereas the other 10strains (“10-mix”) weakly induced IFNγ+CD8+ T cells compared to thelevels induced by the 11-mix (FIGS. 12A and 12B). Mice inoculated with amixture of 17 Treg-inducing bacterial strains (See e.g., WO2013/080561;Atarashi et al., Nature (2013) 500 (7461): 232-236; Narushima et al. GutMicrobes (2014)5(3): 333-339) did not accumulate IFNγ+CD8+ T cells(FIGS. 12A and 12B). A phylogenetic comparison using 16S rRNA genesequences showed that the 11 strain mixture (also referred to as “the 11mix”) consists of 7 strains falling within Bacteroidales (“7 strains”)and 4 strains of non-Bacteroidales: 2 Clostridiales, 1 Fusobacterialesand 1 Selenomonadales (“4 strains”) (See FIG. 13 and Table 4).

Inoculation with the mixture of 4 non-Bacteroidales strains (“4-mix”)resulted in a strong accumulation of colonic IFNγ+CD8+ T cells,comparable to the level of colonic IFNγ+CD8+ T cells observed in micecolonized with the 11 mix. In contrast, colonization with 7Bacteroidales strains (“7-mix”) weakly induced IFNγ+CD8+ T cells (FIGS.14A and 14B). A repeat of the experiment is shown in FIG. 47, whichshows that the 11-mix is more effective than either the 7-mix or the4-mix. The data of the experiment shown in FIG. 47 have strongstatistical support. Identification of the bacterial species with thehighest homology to each of the strains in the 4 mix is provided inTable 4, below.

TABLE 4 Mixture of 4 strains NCBI SEQ ID of accession # NCBI 16S Strain# SEQ ID NO Strain ID Species with highest homology of 16S locus locus 11 2G5 Phascolarctobacterium faecium LN998073 27 2 2 1A6 Fusobacteriumulcerans KR822463 28 5 5 2B1 Subdoligranulum sp. KM098109 31 10 10 1C1Eubacterum limosum NR113248 36

Example 3: Anti-Cancer Characteristics of CD8+ T-Cell Inducing BacterialCocktail

To investigate whether colonization with the 11 mix could enhanceanticancer immune responses, a subcutaneous tumor model was used. SPFmice were treated with mixture of antibiotics (1 g/L ampicillin, 0.5 g/Lvancomycin, 1 g/L metronidazole, and 1 g/L neomycin) via the drinkingwater from day −7 to day 2. A MC38 colon cancer cell line (3×105 cellsper mouse) was subcutaneously injected into the right flank of mice atday 0. Antibiotics treatment was stopped at day 2, and mice were gavagedwith fecal microbiota from SPF mice mixed with or without 11-mix on day3. For the 11-mix treatment groups, mice were gavaged with the 11 mixtwo or three times per week until the end of the experiment. For theanti-PD-1 antibody (Ab) treatment groups, mice were intraperitoneallyinjected with 200μg of anti-PD1 monoclonal Ab (clone J43) at days 3, 5and 9. Tumor size was measured using a caliper and tumor volume wasdetermined as length×width 2×0.5.

Treatment with the 11 mix alone (i.e., without anti-PD1 Ab)significantly suppressed MC38 tumor growth (see FIG. 15). Thecombination of the 11 mix and anti-PD1 Ab exhibited the strongestsuppressive effect on the growth of tumor cells (see FIG. 15). Treatmentwith the 11 mix and anti-PD1 Ab resulted in elevated accumulation ofIFNγ+CD8+ T cells in the MC38 tumor mass (see FIGS. 16A and 16B). Asubset of the IFNγ+CD8+ T cells in tumors expressed T-cell receptorsspecific for gp70p15E604-611 (KSPWFTTL; SEQ ID NO; 53), which is animmunodominant epitope of MC38 (FIG. 17A). Furthermore, a subset ofIFNγ+CD8+ T cells expressed CD44 and Granzyme B, suggesting that theIFNγ+CD8+ T cells accumulated in the tumor included tumor-specific andmemory-type cytotoxic CD8+ T cells (see FIGS. 17A and 17B). The effecton IFNγ+CD4 T cells is shown in FIG. 18. Oral inoculation with the 11mix resulted in the increased numbers of IFNγ-producing splenocytes,even in the absence of tumor antigen stimulation (see FIG. 19).

These results show that treatment with 11 mix in combination with, orwithout, anti-PD1 Ab systemically activate CD8 T cells that respond totumor cells.

Example 4: Anti-Cancer Characteristics of CD8+ T-Cell Inducing BacterialCocktail in Combination with CTLA-4 Immune Checkpoint Inhibitor

To investigate whether colonization with the 11-mix in combination withimmune checkpoint inhibitor CTLA4 could enhance anticancer immuneresponse, a subcutaneous tumor model was used (FIG. 24). Mice weretreated with mixture of antibiotics for 5 days (from day −21 to day−16), followed by a two-day period to wash out the antibiotics. A MC38colon cancer cell line (3×105 cells per mouse) was subcutaneouslyinjected into the right flank of mice at day −14. The animals wererandomized into the following treatment groups:

Group 1: No antibiotics, no treatments (provides a reference forstandard progression of MC38 tumor model);

Group 2: Antibiotic pre-treatment, no treatment (provides a referencefor the progression of the MC38 tumor model with antibioticpre-treatment);

Group 3: 11-mix monotherapy (referred to as AAM1 in FIGS. 25 and 26);

Group 8: anti-CTLA-4 antibody (9H10) and 11-mix (referred to as AAM1 inFIGS. 25 and 26) combination;

Group 9: anti-CTLA-4 antibody (9H10) monotherapy. Bacterial cocktailtreatments were also begun on day −14 and administered biweekly 4 times.For groups receiving the CTLA-4 immune checkpoint inhibitor, thetreatment was begun once the tumor volume reached approximately 100 mm3(100-150 mm3). The anti-CTLA-4 antibody was administered on days 1, 4,and 7. The mice were assessed for weight and survival through the courseof the experiment. Tumor size and volume were measured.Tumor Measurements

The group of mice that received the anti-CTLA-4 antibody alone (Group 9)had slightly reduced tumor growth compared to control mice. Thecombination of the 11-mix (referred to as “AAM1” in FIG. 25) and theanti-CTLA-4 antibody (Group 8) significantly reduced the tumor growth ascompared to the 11-mix on its own and as compared to the anti-CTLA-4antibody on its own. See FIG. 25. Tumor volume plots of individual miceare shown in FIG. 27.

Survival

The group of mice that received the anti-CTLA-4 antibody alone hadslightly increased survival compared to control mice. The 11-mix byitself had no impact on survival. The combination of the 11-mix(referred to as “AAM1” in FIG. 26) and the anti-CTLA-4 antibodysignificantly enhanced survival of the treated mice (Group 8). See FIG.26.

Example 5: Anti-Cancer Characteristics of CD8+ T-Cell Inducing BacterialCocktails in Combination with an Anti-PD1 Antibody

To investigate whether colonization with the 4-mix or 11-mix incombination with immune checkpoint inhibitor anti-PD1 could enhanceanticancer immune responses in the absence of antibiotic pretreatmentand prior engraftment, a MC38 colon cancer cell line (3×105 cells permouse) was subcutaneously injected into the right flank of mice at day−14 (See FIG. 28). The animals were randomized into the followingtreatment groups:

Group 1: No treatment;

Group 3: 11-mix monotherapy (referred to as “AAM1” in FIGS. 28 and 29);

Group 4: 4-mix monotherapy (referred to as “AAM2” in FIGS. 28 and 29);

Group 5: anti-PD1 antibody (RMP1-14) monotherapy;

Group 6: anti-PD1 antibody (RMP1-14) and 11-mix (referred to as “AAM1”in FIGS. 28 and 29) combination; and

Group 7: anti-PD1 antibody (RMP1-14) and 4-mix (referred to as “AAM2” inFIGS. 28 and 29) combination.

The treatments were begun at day 1 (tumor volume approximately 100-150mm3). Bacterial cocktail treatment and the anti-PD1 antibody wereadministered biweekly twice. The mice were assessed for weight andsurvival through the course of the experiment. Tumor size and volumewere measured.

Tumor Measurement

Treatment with the anti-PD1 antibody alone or in combination with eitherthe 4-mix or the 11-mix resulted in a reduction in tumor growth ascompared to no treatment. FIG. 30 shows tumor volume plots of theindividual mice treated in experiments of Example 5 (control, 11-mix;αPD-1 Ab; 11-mix+αPD-1 Ab). The tumor volume did not increase inmultiple animals in the 11-mix+αPD-1 Ab treatment group (bottom rightpanel). FIG. 32 shows tumor volume plots of individual mice treated inexperiments of Example 5 (control, 4-mix; αPD-1 Ab; 4-mix+αPD-1 Ab). Thetumor volume did not increase in multiple animals in the 4-mix+αPD-1 Abtreatment group (bottom right panel).

Survival

Survival data are shown in FIG. 31 for the control, 11-mix; PD-1 Ab; and11-mix+PD-1 Ab groups. The combination of the 11-mix and the αPD-1 Abshowed increased survival when compared to either the 11-mix or theαPD-1 Ab on its own. The combined survival data of mice in the control,4-mix; αPD-1 Ab; 4-mix+αPD-1 Ab, 11-mix, and 11-mix+αPD-1 Ab groups areshown in FIG. 33. Both the combination of the 4-mix and the αPD-1 Ab andthe combination of the 11-mix and the αPD-1 antibody showed increasedsurvival when compared to the αPD-1 Ab on its own.

Example 6: Anti-Cancer Characteristics of CD8+ T-Cell Inducing BacterialCocktail Combination with an Anti-PD1 Antibody in a Melanoma Model

A melanoma engraftment mouse model was used to evaluate the efficacy ofthe 11-mix in combination with a PD-1 antibody in the treatment ofmelanoma. As shown in the timelines in FIGS. 34 and 35, mice receivedantibiotics (Ampicillin, Vancomycin, Metronidazole, and Neomycin:“AVMN”) from day −3 to day 2. On day 0, the mice were engrafted with7×105 Braf Pten melanoma cells. The mice were grouped in the followingtreatment groups:

-   -   Specific Pathogen Free (SPF) feces;    -   SPF feces+anti-PD1 antibody;    -   SPF feces+11-mix; and    -   SPF feces+11-mix+anti-PD1 antibody. On days 3, 6, and 9, the        mice were administered SLC SPF feces from specific-pathogen free        (SPF) mice obtained from Japan SLC (SLC SPF feces), an anti-PD1        antibody (arrows on the timelines in FIGS. 34 and 35) and/or the        11-mix (arrows with asterisk on the timelines in FIGS. 34 and        35). The 11-mix was administered to the indicated groups of mice        2 or 3 times per week by gavage. Mice that received the        combination of the anti-PD1 antibody and the 11-mix had reduced        tumor volume (FIG. 34), tumor area (FIG. 35), and tumor weight        (FIG. 36) as compared to the other groups of mice.

Lymphocytes were isolated from tumors obtained from the mice on days 22and 24 and stained using antibodies to cell markers, including CD3,TCRβ, CD8, CD4, IFNγ, Granzyme, and IL-17. Treatment with the 11-mix andanti-PD1 antibody combination resulted in elevated accumulation ofIFNγ+CD8+ T cells in the melanoma tumor. FIGS. 37A-37C and 38. In thisexperiment, there was no significant difference in the number ofIFNγ+GzmB+ cells, Th1 cells, Th17 cells, or Treg cells between thegroups of mice. FIGS. 39A-39D.

These results show that treatment with 11-mix in combination with theanti-PD1 antibody systemically activates CD8 T cells in the melanoma.

Example 7: CD8 T-Cell Induction in Specific-Pathogen Free (SPF) Mice

Experimental parameters were evaluated for the induction of CD8 T cellsby the 11-mix bacterial cocktail. The animals used in this study werespecific pathogen free mice (SPF mice) as compared to germ-free mice.

As shown in FIG. 40, the mice were grouped in the following treatmentgroups:

-   -   11-mix multi-dose;    -   AVMN+SPF feces;    -   AVMN+SPF feces+11-mix single dose; and    -   AVMN+SPF feces+11-mix multi-dose. The indicated groups of mice        received antibiotics (Ampicillin, Vancomycin, Metronidazole, and        Neomycin: “AVMN”) in their drinking water from day −5 to day −1.        Mice were inoculated with SPF feces with or without the 11-mix        on day 0. For groups that received multiple doses of the 11-mix,        the bacterial cocktail was also administered in the water on        days 3, 7, 10, 14, 17, 21, 24, and 28.

Lymphocytes were isolated from the mice on days 22 and 24 and stainedusing antibodies to cell markers, including CD3, TCRβ, CD8, CD4, IFNγ,Granzyme, and IL-17. Mice that received the antibiotic pretreatment andmultiple doses of the 11-mixed showed enhanced levels of IFNγ+CD8+ Tcells. FIGS. 41A-41C. The mice that received the antibiotic pretreatmentand multiple doses of the 11-mixes also had enhanced levels of CD103+IFNγ+ cells in the CD8T cell population of cells (FIG. 42A) and slightlyenhanced levels of Th17 cells (FIG. 42B). There was no significantdifference in the number of Th1 cells between the groups of mice. (FIG.42C). These data show that the 11-mix can induce CD8+ T cells in acomplex background: a specific pathogen free mouse (as compared to agerm free mouse).

Example 8: The Role of Transcription Factor BATF3

The 11-mix was administered to mice that have the BATF3 transcriptionfactor and mice that do not have the BATF3 transcription factor. Micethat do not have the transcription factor BATF3 are not susceptible toCD8 T cell induction by the 11-mix. (FIGS. 43A and 43B). It is likelythat CD103-CD11b dendritic cells are required for stimulation ofIFNγ-producing CD8 and Th1 cells. The induction of Th17 cells by the11-mix cocktail is independent of BAFT3 status. (FIG. 43C). FIGS. 43 and44 show the results from the experiments of Example 8. The experimentsshow that BATF3 is required for the 11-mix to induce CD8−T cells. BATF3is not required to induce Th17.

Example 9: Treatment of Listeria Infected Mice

Since IFNγ+CD8+ T cells have been reported to play critical roles incontrolling intracellular pathogens, it was evaluated whether oralsupplementation with the 11 strain mixture in a multiple dosing regimencould augment host protective immunity against Listeria monocytogenesinfection. SPF mice were treated with AVMN (ampicillin, vancomycin,metronidazole, neomycin) for 5 days via the drinking water. After oneday washout of antibiotics, multiple oral administrations of the 11-mix(4 times) were performed. To reconstitute complex microbiota, fecalmicrobiota from SPF mice were introduced together with the firstadministration of 11-mix. The mice were then orally infected withListeria monocytogenes on day 0. Fecal Listeria CFU and body weight ofmice were determined. Treatment with 11-mix significantly reducedListeria monocytogenes colonization of the gut lumen (FIG. 45) andmaintained the body weight of the mice (FIG. 46). Thus, administrationof the 11 strain-mixture can provide protective immunity against anintracellar, infectious pathogen.

Example 10: Localization of the CD8 T-Cells Induced by the 11-Mix

The 11-mix was administered to normal healthy mice (i.e., mice that werenot otherwise stressed). Various organs and compartments in the micewere investigated for the presence of CD8 positive T-cells. As shown inFIG. 48, the CD8 positive T-cell induction effect of the 11-mix islimited to the intestine/gut (SI=small intestine, CIEL=colonicintraepithelial lymphocytes, LN=lymph nodes).

Example 11: Selective and Temporal Activation of Subsets of LaminaPropria Dendritic Cells

As CD8 cells can be activated through certain subclasses of dendriticcells, the number and activation state of lamina propria CD11b− CD103+dendritic cells was investigated following administration of the 11-mix.As shown in FIG. 49, the administration of the 11-mix did not change theproportion of the lamina propria CD11b− CD103+ dendritic cell subset.The temporality/kinetics of activation was also investigated. GF micewere colonized with the 11-mix for 1, 2, 3, and 4 weeks. The frequencyof colonic LP and MLN dendritic cells (DCs)/macrophage subsets were notaffected by the colonization with 11 mix. However, expression of MHCclass I on colonic LP DCs (but not MLN DCs), particularly on colonic LPCD103+ DC subset (namely, Batf3-dependent DC subset), was significantlyenhanced by the colonization with 11-mix. Upregulation of MHC class Iexpression most strongly occurred at 1 week after colonization. (SeeFIGS. 50-54) Without being limited to a particular mechanism it islikely that induction of the CD8 positive T cells is mostly due toproliferation rather than antigen-specific de novo differentiation. Ki67staining revealed that expansion of CD8 positive T cells occurred at 1week, accompanied by increase with IFNγ+CD8+ T in the colonic LP (SeeFIG. 55). CD103 staining revealed that induced IFNγ+CD8+ T at 1 weekpost colonization were mostly CD103 negative, and that CD103+ IFNγ+CD8 T(tissue resident memory phenotype CD8+ T) were gradually increased (SeeFIGS. 56 and 57).

SEQUENCE LISTING

Sequence_List.TXT

The invention claimed is:
 1. A method for treating cancer in a subjectundergoing cancer immunotherapy, the method comprising administering tothe subject a pharmaceutical composition comprising a purified bacterialmixture consisting of bacterial strains comprising 16S rDNA sequences ofat least 99% sequence identity with SEQ ID NO:1, SEQ ID NO:2, SEQ IDNO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8,SEQ ID NO:9, SEQ ID NO:10, and SEQ ID NO:11, in a therapeuticallyeffective amount to treat the cancer, wherein the pharmaceuticalcomposition is formulated for delivery to the intestine of the subject.2. The method of claim 1, wherein said cancer immunotherapy comprisesadministering an anti-cancer agent to the subject.
 3. The method ofclaim 2, wherein the anti-cancer agent is an immune checkpointinhibitor.
 4. The method of claim 3, wherein the immune checkpointinhibitor is a PD-1 inhibitor.
 5. The method of claim 3, wherein theimmune checkpoint inhibitor is nivolumab.
 6. The method of claim 3,wherein the immune checkpoint inhibitor is pembrolizumab.
 7. The methodof claim 3, wherein the immune checkpoint inhibitor is a CTLA-4inhibitor.
 8. The method of claim 1, further comprising administering anantibiotic prior to administering the pharmaceutical composition oradministering multiple doses of an antibiotic prior to administering thepharmaceutical composition.
 9. The method of claim 8, wherein theantibiotic is kanamycin, gentamicin, colistin, metronidazole,vancomycin, clindamycin, fidaxomicin or cefoperazone.
 10. The method ofclaim 9, wherein the antibiotic is vancomycin.
 11. The method of claim1, wherein the cancer is a carcinoma or an adenocarcinoma.
 12. Themethod of claim 1, wherein the cancer is melanoma, head and neck cancer,stomach cancer, esophageal cancer, non-small cell lung cancer orcolorectal cancer.
 13. The method of claim 12, wherein the cancer ishead and neck cancer.
 14. The method of claim 12, wherein the cancer isstomach cancer.
 15. The method of claim 12, wherein the cancer isesophageal cancer.
 16. The method of claim 12, wherein the cancer isnon-small cell lung cancer.
 17. The method of claim 12, wherein thecancer is colorectal cancer.
 18. The method of claim 5, furthercomprising administering an antibiotic prior to administering thepharmaceutical composition.
 19. The method of claim 18, wherein theantibiotic is vancomycin.
 20. The method of claim 12, wherein the canceris melanoma.